{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:48:47Z","timestamp":1790786927490,"version":"4.1.0"},"reference-count":211,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della salute Ricerca Corrente","award":["AIRC IG 21648"],"award-info":[{"award-number":["AIRC IG 21648"]}]},{"name":"Ministero della salute Ricerca Corrente","award":["ROL 32567"],"award-info":[{"award-number":["ROL 32567"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["AIRC IG 21648"],"award-info":[{"award-number":["AIRC IG 21648"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["ROL 32567"],"award-info":[{"award-number":["ROL 32567"]}]},{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["AIRC IG 21648"],"award-info":[{"award-number":["AIRC IG 21648"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["ROL 32567"],"award-info":[{"award-number":["ROL 32567"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Therefore, the need for new therapeutic strategies is still a challenge. Surgery and chemotherapy represent the first-line interventions; nevertheless, the prognosis for metastatic CRC (mCRC) patients remains unacceptable. An important step towards targeted therapy came from the inhibition of the epidermal growth factor receptor (EGFR) pathway, by the anti-EGFR antibody, Cetuximab, or by specific tyrosine kinase inhibitors (TKI). Cetuximab, a mouse\u2013human chimeric monoclonal antibody (mAb), binds to the extracellular domain of EGFR thus impairing EGFR-mediated signaling and reducing cell proliferation. TKI can affect the EGFR biochemical pathway at different steps along the signaling cascade. Apart from Cetuximab, other anti-EGFR mAbs have been developed, such as Panitumumab. Both antibodies have been approved for the treatment of KRAS-NRAS wild type mCRC, alone or in combination with chemotherapy. These antibodies display strong differences in activating the host immune system against CRC, due to their different immunoglobulin isotypes. Although anti-EGFR antibodies are efficient, drug resistance occurs with high frequency. Resistant tumor cell populations can either already be present before therapy or develop later by biochemical adaptations or new genomic mutations in the EGFR pathway. Numerous efforts have been made to improve the efficacy of the anti-EGFR mAbs or to find new agents that are able to block downstream EGFR signaling cascade molecules. Indeed, we examined the importance of analyzing the anti-EGFR antibody\u2013drug conjugates (ADC) developed to overcome resistance and\/or stimulate the tumor host\u2019s immunity against CRC growth. Also, patient-derived CRC organoid cultures represent a useful and feasible in vitro model to study tumor behavior and therapy response. Organoids can reflect tumor genetic heterogeneity found in the tissue of origin, representing a unique tool for personalized medicine. Thus, CRC-derived organoid cultures are a smart model for studying the tumor microenvironment and for the preclinical assay of anti-EGFR drugs.<\/jats:p>","DOI":"10.3390\/ijms25137131","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance"],"prefix":"10.3390","volume":"25","author":[{"given":"Samuele","family":"Tardito","sequence":"first","affiliation":[{"name":"Center for Cancer and Immunology Research, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-0213","authenticated-orcid":false,"given":"Serena","family":"Matis","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRRCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Raffaella","family":"Zocchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Transplant and Infectious Diseases, IRCCS Scientific Institute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9769-0954","authenticated-orcid":false,"given":"Roberto","family":"Benelli","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRRCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-430X","authenticated-orcid":false,"given":"Alessandro","family":"Poggi","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRRCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.4240\/wjgs.v15.i4.495","article-title":"Current and Emerging Therapeutic Approaches for Colorectal Cancer: A Comprehensive Review","volume":"15","author":"Kumar","year":"2023","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJMra2200869","article-title":"Increasing Incidence of Early-Onset Colorectal Cancer","volume":"386","author":"Sinicrope","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41392-020-0116-z","article-title":"Comprehensive Review of Targeted Therapy for Colorectal Cancer","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3892\/or.2023.8537","article-title":"Immunotherapy: A New Target for Cancer Cure (Review)","volume":"49","author":"Zhao","year":"2023","journal-title":"Oncol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41575-019-0126-x","article-title":"Immunotherapy in Colorectal Cancer: Rationale, Challenges and Potential","volume":"16","author":"Ganesh","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A Guide to Cancer Immunotherapy: From T Cell Basic Science to Clinical Practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zahavi, D.J., Erbe, R., Zhang, Y.-W., Guo, T., Malchiodi, Z.X., Maynard, R., Lekan, A., Gallagher, R., Wulfkuhle, J., and Petricoin, E. (2023). Antibody Dependent Cell-Mediated Cytotoxicity Selection Pressure Induces Diverse Mechanisms of Resistance. Cancer Biol. Ther., 24.","DOI":"10.1080\/15384047.2023.2269637"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41392-021-00868-x","article-title":"Emerging New Therapeutic Antibody Derivatives for Cancer Treatment","volume":"7","author":"Jin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18911","DOI":"10.1038\/s41598-019-54849-w","article-title":"Improving the Odds of Drug Development Success through Human Genomics: Modelling Study","volume":"9","author":"Hingorani","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrclinonc.2017.166","article-title":"Tumour Heterogeneity and Resistance to Cancer Therapies","volume":"15","author":"Shaw","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/s41580-020-0259-3","article-title":"Human Organoids: Model Systems for Human Biology and Medicine","volume":"21","author":"Kim","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hockney, S., Parker, J., Turner, J.E., Todd, X., Todryk, S., Gieling, R.G., Hilgen, G., Simoes, D.C.M., and Pal, D. (2023). Next Generation Organoid Engineering to Replace Animals in Cancer Drug Testing. Biochem. Pharmacol., 213.","DOI":"10.1016\/j.bcp.2023.115586"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e274","DOI":"10.1002\/mco2.274","article-title":"Organoids: The Current Status and Biomedical Applications","volume":"4","author":"Yang","year":"2023","journal-title":"MedComm"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/gastro\/goaa026","article-title":"Anti-EGFR Therapy in Metastatic Colorectal Cancer: Mechanisms and Potential Regimens of Drug Resistance","volume":"8","author":"Li","year":"2020","journal-title":"Gastroenterol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wee, P., and Wang, Z. (2017). Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers, 9.","DOI":"10.3390\/cancers9050052"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1517\/13543781003593962","article-title":"Colorectal Cancer in Review: The Role of the EGFR Pathway","volume":"19","author":"Saif","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.biophys.37.032807.125829","article-title":"Structure-Based View of Epidermal Growth Factor Receptor Regulation","volume":"37","author":"Ferguson","year":"2008","journal-title":"Annu. Rev. Biophys."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Uribe, M.L., Marrocco, I., and Yarden, Y. (2021). EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers, 13.","DOI":"10.3390\/cancers13112748"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1074\/jbc.M209148200","article-title":"Epidermal Growth Factor Receptor Mediates Increased Cell Proliferation, Migration, and Aggregation in Esophageal Keratinocytes in Vitro and in Vivo","volume":"278","author":"Andl","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0092-8674(92)90167-B","article-title":"The SH2 and SH3 Domain-Containing Protein GRB2 Links Receptor Tyrosine Kinases to Ras Signaling","volume":"70","author":"Lowenstein","year":"1992","journal-title":"Cell"},{"key":"ref_21","first-page":"5192","article-title":"Hierarchy of Binding Sites for Grb2 and Shc on the Epidermal Growth Factor Receptor","volume":"14","author":"Batzer","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nrm1834","article-title":"MAPKAP Kinases\u2014MKs\u2014Two\u2019s Company, Three\u2019s a Crowd","volume":"7","author":"Gaestel","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc839","article-title":"The Phosphatidylinositol 3-Kinase\u2013AKT Pathway in Human Cancer","volume":"2","author":"Vivanco","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/sj.onc.1205260","article-title":"Constitutive Stat3 Activity Up-Regulates VEGF Expression and Tumor Angiogenesis","volume":"21","author":"Niu","year":"2002","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI0215617","article-title":"Stat Proteins and Oncogenesis","volume":"109","author":"Bromberg","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/jcb.21475","article-title":"STAT-mediated EGFR Signaling in Cancer","volume":"102","author":"Quesnelle","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.tibs.2005.10.005","article-title":"Phospholipase C-\u03b3: Diverse Roles in Receptor-Mediated Calcium Signaling","volume":"30","author":"Patterson","year":"2005","journal-title":"Trends Biochem. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1128\/MCB.18.2.790","article-title":"Activation of the Mitogen-Activated Protein Kinase\/Extracellular Signal-Regulated Kinase Pathway by Conventional, Novel, and Atypical Protein Kinase C Isotypes","volume":"18","author":"Marais","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4161\/cl.21882","article-title":"PAK Signaling in Cancer","volume":"2","author":"Ye","year":"2012","journal-title":"Cell. Logist."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.devcel.2010.01.013","article-title":"A PAK-Activated Linker for EGFR and FAK","volume":"18","author":"Tomar","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_31","first-page":"867","article-title":"Cbl-b Regulates the Sensitivity of Cetuximab through Ubiquitin-Proteasome System in Human Gastric Cancer Cells","volume":"21","author":"Yu","year":"2016","journal-title":"J. Buon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1158\/0008-5472.CAN-15-0989","article-title":"Ligand-Independent EGFR Signaling","volume":"75","author":"Guo","year":"2015","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Z. (2016). Transactivation of Epidermal Growth Factor Receptor by G Protein-Coupled Receptors: Recent Progress, Challenges and Future Research. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010095"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.bbrc.2016.07.097","article-title":"Effects of Different Ligands on Epidermal Growth Factor Receptor (EGFR) Nuclear Translocation","volume":"478","author":"Faria","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ccr.2005.05.007","article-title":"Nuclear Interaction of EGFR and STAT3 in the Activation of the iNOS\/NO Pathway","volume":"7","author":"Lo","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1158\/0008-5472.338.65.1","article-title":"Novel Prognostic Value of Nuclear Epidermal Growth Factor Receptor in Breast Cancer","volume":"65","author":"Lo","year":"2005","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1158\/1078-0432.CCR-14-0848","article-title":"Molecular Pathways: Sensitivity and Resistance to Anti-EGFR Antibodies","volume":"21","author":"Bertotti","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Foncillas, J., Sunakawa, Y., Aderka, D., Wainberg, Z., Ronga, P., Witzler, P., and Stintzing, S. (2019). Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00849"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1158\/0008-5472.CAN-09-0049","article-title":"Cetuximab\/C225-Induced Intracellular Trafficking of Epidermal Growth Factor Receptor","volume":"69","author":"Liao","year":"2009","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1073\/pnas.83.11.3825","article-title":"Monoclonal Antibody against Epidermal Growth Factor Receptor Is Internalized without Stimulating Receptor Phosphorylation","volume":"83","author":"Sunada","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ccr.2005.03.003","article-title":"Structural Basis for Inhibition of the Epidermal Growth Factor Receptor by Cetuximab","volume":"7","author":"Li","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Baysal, H., De Pauw, I., Zaryouh, H., Peeters, M., Vermorken, J.B., Lardon, F., De Waele, J., and Wouters, A. (2021). The Right Partner in Crime: Unlocking the Potential of the Anti-EGFR Antibody Cetuximab via Combination With Natural Killer Cell Chartering Immunotherapeutic Strategies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.737311"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/156800910790980241","article-title":"CETUXIMAB: From Bench to Bedside","volume":"10","author":"Vincenzi","year":"2010","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Doleschal, B., Petzer, A., and Rumpold, H. (2022). Current Concepts of Anti-EGFR Targeting in Metastatic Colorectal Cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1048166"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/nbt1337","article-title":"From XenoMouse Technology to Panitumumab, the First Fully Human Antibody Product from Transgenic Mice","volume":"25","author":"Jakobovits","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ros, J., Vaghi, C., Baraibar, I., Saoudi Gonz\u00e1lez, N., Rodr\u00edguez-Castells, M., Garc\u00eda, A., Alcaraz, A., Salva, F., Tabernero, J., and Elez, E. (2024). Targeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063304"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41392-021-00780-4","article-title":"KRAS Mutation: From Undruggable to Druggable in Cancer","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/s41591-024-02903-0","article-title":"Targeting KRAS in Cancer","volume":"30","author":"Singhal","year":"2024","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1158\/0008-5472.CAN-06-0191","article-title":"KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer","volume":"66","author":"Bachet","year":"2006","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100745","DOI":"10.1016\/j.esmoop.2022.100745","article-title":"Targeting KRASG12C in Colorectal Cancer: The Beginning of a New Era","volume":"8","author":"Ciardiello","year":"2023","journal-title":"ESMO Open"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1158\/2159-8290.CD-20-0187","article-title":"EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer","volume":"10","author":"Amodio","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1023\u2013IN3","DOI":"10.1593\/neo.121242","article-title":"Functional Dissection of the Epidermal Growth Factor Receptor Epitopes Targeted by Panitumumab and Cetuximab","volume":"14","author":"Voigt","year":"2012","journal-title":"Neoplasia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1158\/1535-7163.MCT-11-1038","article-title":"Impact of Intrinsic Affinity on Functional Binding and Biological Activity of EGFR Antibodies","volume":"11","author":"Zhou","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1476-4598-9-139","article-title":"Complement Activation Mediates Cetuximab Inhibition of Non-Small Cell Lung Cancer Tumor Growth in Vivo","volume":"9","author":"Hsu","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1158\/2326-6066.CIR-15-0184","article-title":"Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy","volume":"4","author":"Trotta","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zubair, T., and Bandyopadhyay, D. (2023). Small Molecule EGFR Inhibitors as Anti-Cancer Agents: Discovery, Mechanisms of Action, and Opportunities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032651"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/annonc\/mdx702","article-title":"Overview of Current Systemic Management of EGFR-Mutant NSCLC","volume":"29","author":"Hsu","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev.med.55.091902.104433","article-title":"The erbB Family: Targets for Therapeutic Development Against Cancer and Therapeutic Strategies Using Monoclonal Antibodies and Tyrosine Kinase Inhibitors","volume":"55","author":"Rowinsky","year":"2004","journal-title":"Annu. Rev. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1200\/JCO.21.02911","article-title":"Updated Analysis of NEJ009: Gefitinib-Alone Versus Gefitinib Plus Chemotherapy for Non\u2013Small-Cell Lung Cancer With Mutated EGFR","volume":"40","author":"Miyauchi","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.3816\/CCC.2005.s.009","article-title":"Current Status of Small-Molecule Tyrosine Kinase Inhibitors Targeting Epidermal Growth Factor Receptor in Colorectal Cancer","volume":"5","author":"Kuo","year":"2005","journal-title":"Clin. Color. Cancer"},{"key":"ref_61","first-page":"CD007047","article-title":"Epidermal Growth Factor Receptor (EGFR) Inhibitors for Metastatic Colorectal Cancer","volume":"6","author":"Chan","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13046-021-02130-2","article-title":"Resistance to Anti-EGFR Therapies in Metastatic Colorectal Cancer: Underlying Mechanisms and Reversal Strategies","volume":"40","author":"Zhou","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1038\/nm.3388","article-title":"The Quest to Overcome Resistance to EGFR-Targeted Therapies in Cancer","volume":"19","author":"Chong","year":"2013","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e175245","DOI":"10.1001\/jamaoncol.2017.5245","article-title":"Efficacy of Sym004 in Patients With Metastatic Colorectal Cancer With Acquired Resistance to Anti-EGFR Therapy and Molecularly Selected by Circulating Tumor DNA Analyses: A Phase 2 Randomized Clinical Trial","volume":"4","author":"Montagut","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13665","DOI":"10.1038\/ncomms13665","article-title":"Acquired RAS or EGFR Mutations and Duration of Response to EGFR Blockade in Colorectal Cancer","volume":"7","author":"Arena","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nm.2609","article-title":"Identification of a Mutation in the Extracellular Domain of the Epidermal Growth Factor Receptor Conferring Cetuximab Resistance in Colorectal Cancer","volume":"18","author":"Montagut","year":"2012","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S1470-2045(05)70102-9","article-title":"Gene Copy Number for Epidermal Growth Factor Receptor (EGFR) and Clinical Response to antiEGFR Treatment in Colorectal Cancer: A Cohort Study","volume":"6","author":"Moroni","year":"2005","journal-title":"Lancet Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1200\/JCO.2007.11.5956","article-title":"Epidermal Growth Factor Receptor Gene Copy Number and Clinical Outcome of Metastatic Colorectal Cancer Treated With Panitumumab","volume":"25","author":"Moroni","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1756-8722-5-52","article-title":"EGFR Gene Copy Number as a Predictive Biomarker for the Treatment of Metastatic Colorectal Cancer with Anti-EGFR Monoclonal Antibodies: A Meta-Analysis","volume":"5","author":"Yang","year":"2012","journal-title":"J. Hematol. Oncol."},{"key":"ref_70","first-page":"1311","article-title":"Biological Efficacy of a Chimeric Antibody to the Epidermal Growth Factor Receptor in a Human Tumor Xenograft Model","volume":"1","author":"Goldstein","year":"1995","journal-title":"Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1038\/bjc.2012.103","article-title":"Cross-Suppression of EGFR Ligands Amphiregulin and Epiregulin and de-Repression of FGFR3 Signalling Contribute to Cetuximab Resistance in Wild-Type KRAS Tumour Cells","volume":"106","author":"Queralt","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1200\/JCO.2006.10.5437","article-title":"Expression of Epiregulin and Amphiregulin and K-Ras. Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab","volume":"25","author":"Garrett","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11523-013-0284-7","article-title":"EGFR Ligands as Pharmacodynamic Biomarkers in Metastatic Colorectal Cancer Patients Treated with Cetuximab and Irinotecan","volume":"9","author":"Loupakis","year":"2014","journal-title":"Target. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Garvey, C.M., Lau, R., Sanchez, A., Sun, R.X., Fong, E.J., Doche, M.E., Chen, O., Jusuf, A., Lenz, H.-J., and Larson, B. (2020). Anti-EGFR Therapy Induces EGF Secretion by Cancer-Associated Fibroblasts to Confer Colorectal Cancer Chemoresistance. Cancers, 12.","DOI":"10.3390\/cancers12061393"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gimple, R.C., and Wang, X. (2019). RAS: Striking at the Core of the Oncogenic Circuitry. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00965"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/S1470-2045(10)70209-6","article-title":"KRAS, BRAF, PIK3CA, and PTEN Mutations: Implications for Targeted Therapies in Metastatic Colorectal Cancer","volume":"12","author":"Roock","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrc1097","article-title":"RAS Oncogenes: The First 30 Years","volume":"3","author":"Malumbres","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1038\/s41467-019-11530-0","article-title":"Comprehensive Characterization of RAS Mutations in Colon and Rectal Cancers in Old and Young Patients","volume":"10","author":"Serebriiskii","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1200\/JCO.2014.59.4812","article-title":"Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Treatment and RAS Mutations in Colorectal Cancer","volume":"33","author":"Lenz","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1200\/EDBK_349561","article-title":"The Evolving Treatment Landscape in BRAF-V600E \u2013Mutated Metastatic Colorectal Cancer","volume":"42","author":"Tabernero","year":"2022","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1056\/NEJMc0904160","article-title":"BRAF Mutation in Metastatic Colorectal Cancer","volume":"361","author":"Tol","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1056\/NEJMoa1908075","article-title":"Encorafenib, Binimetinib, and Cetuximab in BRAF V600E\u2013Mutated Colorectal Cancer","volume":"381","author":"Kopetz","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3892\/or.2021.8222","article-title":"PIK3CA Mutation Affects the Proliferation of Colorectal Cancer Cells through the PI3K-MEK\/PDK1-GPT2 Pathway","volume":"47","author":"Chen","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Cathomas, G. (2014). PIK3CA in Colorectal Cancer. Front. Oncol., 4.","DOI":"10.3389\/fonc.2014.00035"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Salvatore, L., Calegari, M.A., Loupakis, F., Fassan, M., Di Stefano, B., Bensi, M., Bria, E., and Tortora, G. (2019). PTEN in Colorectal Cancer: Shedding Light on Its Role as Predictor and Target. Cancers, 11.","DOI":"10.3390\/cancers11111765"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1038\/s41467-022-29227-2","article-title":"Comprehensive Characterization of PTEN Mutational Profile in a Series of 34,129 Colorectal Cancers","volume":"13","author":"Serebriiskii","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ccr.2014.05.019","article-title":"Drug Resistance via Feedback Activation of Stat3 in Oncogene-Addicted Cancer Cells","volume":"26","author":"Lee","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"926","DOI":"10.3892\/or.2017.5734","article-title":"Cetuximab Promotes SN38 Sensitivity via Suppression of Heat Shock Protein 27 in Colorectal Cancer Cells with Wild-Type RAS","volume":"38","author":"Ishida","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.18632\/oncotarget.14012","article-title":"Mechanisms of Resistance to Anti-EGFR Therapy in Colorectal Cancer","volume":"8","author":"Zhao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Gargalionis, A.N., Papavassiliou, K.A., and Papavassiliou, A.G. (2021). Targeting STAT3 Signaling Pathway in Colorectal Cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081016"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cell.2010.02.027","article-title":"A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations","volume":"141","author":"Sharma","year":"2010","journal-title":"Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1158\/2159-8290.CD-22-0111","article-title":"AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer","volume":"12","author":"Noronha","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1128\/MCB.01153-14","article-title":"Both High-Fidelity Replicative and Low-Fidelity Y-Family Polymerases Are Involved in DNA Rereplication","volume":"35","author":"Sekimoto","year":"2015","journal-title":"Mol. Cell. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1038\/s41598-019-39762-6","article-title":"Impact of Polymerase Fidelity on Background Error Rates in Next-Generation Sequencing with Unique Molecular Identifiers\/Barcodes","volume":"9","author":"Filges","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1158\/1078-0432.CCR-13-1354","article-title":"AXL Is a Key Regulator of Inherent and Chemotherapy-Induced Invasion and Predicts a Poor Clinical Outcome in Early-Stage Colon Cancer","volume":"20","author":"Dunne","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Gutsch, D., Jenke, R., B\u00fcch, T., and Aigner, A. (2021). Inhibition of HER Receptors Reveals Distinct Mechanisms of Compensatory Upregulation of Other HER Family Members: Basis for Acquired Resistance and for Combination Therapy. Cells, 10.","DOI":"10.3390\/cells10020272"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3892\/ijmm.2021.4847","article-title":"Emerging Trends in Colorectal Cancer: Dysregulated Signaling Pathways (Review)","volume":"47","author":"Ahmad","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Vigneri, P.G., Tirr\u00f2, E., Pennisi, M.S., Massimino, M., Stella, S., Romano, C., and Manzella, L. (2015). The Insulin\/IGF System in Colorectal Cancer Development and Resistance to Therapy. Front. Oncol., 5.","DOI":"10.3389\/fonc.2015.00230"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13046-019-1035-0","article-title":"Receptor Tyrosine Kinase-Dependent PI3K Activation Is an Escape Mechanism to Vertical Suppression of the EGFR\/RAS\/MAPK Pathway in KRAS-Mutated Human Colorectal Cancer Cell Lines","volume":"38","author":"Vitiello","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-020-00904-3","article-title":"Insulin-like Growth Factor Receptor Signaling in Tumorigenesis and Drug Resistance: A Challenge for Cancer Therapy","volume":"13","author":"Hua","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12943-018-0796-y","article-title":"Function of the C-Met Receptor Tyrosine Kinase in Carcinogenesis and Associated Therapeutic Opportunities","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1023\/A:1023051500010","article-title":"No Title Found","volume":"22","author":"Kataoka","year":"2003","journal-title":"Cancer Metastasis Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1038\/s41388-020-01577-5","article-title":"The Role of MET in Chemotherapy Resistance","volume":"40","author":"Wood","year":"2021","journal-title":"Oncogene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.1158\/1078-0432.CCR-13-0423","article-title":"Increased TGF-Alfa as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR\u2013MET Interaction and Activation of MET Signaling in Colon Cancer Cells","volume":"19","author":"Troiani","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1158\/2159-8290.CD-12-0558","article-title":"Amplification of the MET Receptor Drives Resistance to Anti-EGFR Therapies in Colorectal Cancer","volume":"3","author":"Bardelli","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.tcb.2020.07.003","article-title":"EMT, MET, Plasticity, and Tumor Metastasis","volume":"30","author":"Bakir","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7755","DOI":"10.1038\/sj.onc.1203360","article-title":"Ets Transcription Factors Cooperate with Sp1 to Activate the Human Tenascin-C Promoter","volume":"18","author":"Shirasaki","year":"1999","journal-title":"Oncogene"},{"key":"ref_108","first-page":"1911","article-title":"Ets Up-Regulates MET Transcription","volume":"13","author":"Gambarotta","year":"1996","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1535-6108(03)00085-0","article-title":"Hypoxia Promotes Invasive Growth by Transcriptional Activation of the Met Protooncogene","volume":"3","author":"Pennacchietti","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s10585-008-9200-4","article-title":"Kinase Switching in Mesenchymal-like Non-Small Cell Lung Cancer Lines Contributes to EGFR Inhibitor Resistance through Pathway Redundancy","volume":"25","author":"Thomson","year":"2008","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41420-023-01692-8","article-title":"HER-3 Surface Expression Increases in Advanced Colorectal Cancer Representing a Potential Therapeutic Target","volume":"9","author":"Capone","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"99ra86","DOI":"10.1126\/scitranslmed.3002442","article-title":"Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab","volume":"3","author":"Yonesaka","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1158\/1535-7163.MCT-21-0818","article-title":"Triple Targeting of HER Receptors Overcomes Heregulin-Mediated Resistance to EGFR Blockade in Colorectal Cancer","volume":"21","author":"Rau","year":"2022","journal-title":"Mol. Cancer Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1158\/1538-7445.AM2024-2619","article-title":"Abstract 2619: A Novel EGFR \u00d7 HER3-Targeting Bispecific Antibody Drug-Conjugate, BCG019, Demonstrates Robust Anti-Tumor Efficacy in Preclinical Evaluation","volume":"84","author":"Li","year":"2024","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41573-023-00846-8","article-title":"Therapeutic Targeting of the Functionally Elusive TAM Receptor Family","volume":"23","author":"Miao","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejca.2020.07.010","article-title":"AXL Is a Predictor of Poor Survival and of Resistance to Anti-EGFR Therapy in RAS Wild-Type Metastatic Colorectal Cancer","volume":"138","author":"Cardone","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1158\/0008-5472.CAN-14-0294","article-title":"AXL Mediates Resistance to Cetuximab Therapy","volume":"74","author":"Brand","year":"2014","journal-title":"Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1038\/s41467-024-46231-w","article-title":"Distinguishing Preferences of Human APOBEC3A and APOBEC3B for Cytosines in Hairpin Loops, and Reflection of These Preferences in APOBEC-Signature Cancer Genome Mutations","volume":"15","author":"Butt","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41588-023-01592-8","article-title":"The Role of APOBEC3B in Lung Tumor Evolution and Targeted Cancer Therapy Resistance","volume":"56","author":"Caswell","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41392-022-00947-7","article-title":"Antibody Drug Conjugate: The Biological Missile for Targeted Cancer Therapy","volume":"7","author":"Fu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1208\/s12248-014-9710-8","article-title":"Antibody Drug Conjugates: Design and Selection of Linker, Payload and Conjugation Chemistry","volume":"17","author":"McCombs","year":"2015","journal-title":"AAPS J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1001\/jamaoncol.2022.0503","article-title":"Evaluation of Safety of Treatment With Anti\u2013Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors: A Phase 1 Nonrandomized Clinical Trial","volume":"8","author":"Qiu","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yu, J., Fang, T., Yun, C., Liu, X., and Cai, X. (2022). Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.847835"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"S554","DOI":"10.1016\/j.annonc.2023.09.2000","article-title":"854O INTERLINK-1: Phase III Study of Cetuximab (CTX) \u00b1 Monalizumab (M) in Participants (Pts) with Recurrent\/Metastatic Head and Neck Squamous Cell Carcinoma (R\/M HNSCC) with Disease Progression on\/after Platinum Chemotherapy (CT) and Previously Treated with an Immune Checkpoint Inhibitor (ICI)","volume":"34","author":"Fayette","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"S559","DOI":"10.1016\/j.annonc.2023.09.2006","article-title":"860MO MRG003: A Novel EGFR-Targeted Antibody-Drug Conjugant (ADC) for Recurrent\/Metastatic Nasopharyngeal Carcinoma","volume":"34","author":"Han","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"S588","DOI":"10.1016\/j.annonc.2023.09.2079","article-title":"935P A Phase II Study of Monalizumab and Durvalumab in Patients with Recurrent\/Metastatic (RM) Squamous Cell Carcinoma of the Head and Neck (SCCHN): Results of the I2 Cohort of the EORTC-HNCG-1559 Trial (UPSTREAM)","volume":"34","author":"Galot","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1124\/dmd.119.089276","article-title":"Evaluation of Quantitative Relationship Between Target Expression and Antibody-Drug Conjugate Exposure Inside Cancer Cells","volume":"48","author":"Sharma","year":"2020","journal-title":"Drug Metab. Dispos."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"216024","DOI":"10.1016\/j.canlet.2022.216024","article-title":"An Anti-EGFR Antibody-Drug Conjugate Overcomes Resistance to HER2-Targeted Drugs","volume":"554","author":"Pandiella","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1002\/ijc.30870","article-title":"DS-8201a, a New HER2-targeting Antibody\u2013Drug Conjugate Incorporating a Novel DNA Topoisomerase I Inhibitor, Overcomes HER2-positive Gastric Cancer T-DM1 Resistance","volume":"141","author":"Takegawa","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Rodr\u00edguez, E., Gandullo-S\u00e1nchez, L., Oca\u00f1a, A., and Pandiella, A. (2021). Novel ADCs and Strategies to Overcome Resistance to Anti-HER2 ADCs. Cancers, 14.","DOI":"10.3390\/cancers14010154"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.trecan.2019.12.010","article-title":"Trastuzumab Emtansine: Mechanisms of Action and Resistance, Clinical Progress, and Beyond","volume":"6","author":"Pandiella","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1158\/1535-7163.MCT-19-0609","article-title":"Depatuxizumab Mafodotin (ABT-414)-Induced Glioblastoma Cell Death Requires EGFR Overexpression, but Not EGFRY1068 Phosphorylation","volume":"19","author":"Silginer","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1158\/1535-7163.MCT-16-0021","article-title":"A New Triglycyl Peptide Linker for Antibody\u2013Drug Conjugates (ADCs) with Improved Targeted Killing of Cancer Cells","volume":"15","author":"Singh","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.ijbiomac.2020.11.058","article-title":"Bispecific Monoclonal Antibodies for Targeted Immunotherapy of Solid Tumors: Recent Advances and Clinical Trials","volume":"167","author":"Hosseini","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/s41467-023-37029-3","article-title":"An Anti-HER2 Biparatopic Antibody That Induces Unique HER2 Clustering and Complement-Dependent Cytotoxicity","volume":"14","author":"Weisser","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Xie, J., Bi, Y., Zhang, H., Dong, S., Teng, L., Lee, R.J., and Yang, Z. (2020). Cell-Penetrating Peptides in Diagnosis and Treatment of Human Diseases: From Preclinical Research to Clinical Application. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00697"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1039\/D0OB00265H","article-title":"Protein Labeling Approach to Improve Lysosomal Targeting and Efficacy of Antibody\u2013Drug Conjugates","volume":"18","author":"Han","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1007\/s11095-015-1704-4","article-title":"Antibody-Drug Conjugates: Design, Formulation and Physicochemical Stability","volume":"32","author":"Singh","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Pettinato, M.C. (2021). Introduction to Antibody-Drug Conjugates. Antibodies, 10.","DOI":"10.3390\/antib10040042"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Leung, D., Wurst, J., Liu, T., Martinez, R., Datta-Mannan, A., and Feng, Y. (2020). Antibody Conjugates-Recent Advances and Future Innovations. Antibodies, 9.","DOI":"10.3390\/antib9010002"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"111682","DOI":"10.1016\/j.ejmech.2019.111682","article-title":"Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985)","volume":"183","author":"Xu","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1002\/cbic.201900178","article-title":"Recent Chemical Approaches for Site-Specific Conjugation of Native Antibodies: Technologies toward Next-Generation Antibody\u2013Drug Conjugates","volume":"20","author":"Yamada","year":"2019","journal-title":"ChemBioChem"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Khoury, R., Saleh, K., Khalife, N., Saleh, M., Chahine, C., Ibrahim, R., and Lecesne, A. (2023). Mechanisms of Resistance to Antibody-Drug Conjugates. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119674"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Abelman, R.O., Wu, B., Spring, L.M., Ellisen, L.W., and Bardia, A. (2023). Mechanisms of Resistance to Antibody\u2013Drug Conjugates. Cancers, 15.","DOI":"10.3390\/cancers15041278"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e172156","DOI":"10.1172\/JCI172156","article-title":"Antibody-Drug Conjugates in Breast Cancer: Overcoming Resistance and Boosting Immune Response","volume":"133","author":"Chang","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41571-023-00850-2","article-title":"Exploring the next Generation of Antibody\u2013Drug Conjugates","volume":"21","author":"Tsuchikama","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Metrangolo, V., and Engelholm, L.H. (2024). Antibody\u2013Drug Conjugates: The Dynamic Evolution from Conventional to Next-Generation Constructs. Cancers, 16.","DOI":"10.3390\/cancers16020447"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1158\/1078-0432.CCR-23-3414","article-title":"Antibody\u2013Drug Conjugates: Advancing from Magic Bullet to Biological Missile","volume":"30","author":"Veneziani","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"104242","DOI":"10.1016\/j.critrevonc.2023.104242","article-title":"Liquid Biopsy in Colorectal Cancer: Onward and Upward","volume":"194","author":"Torresan","year":"2024","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.currproblcancer.2018.08.004","article-title":"Role of Liquid Biopsies in Colorectal Cancer","volume":"42","author":"Wills","year":"2018","journal-title":"Curr. Probl. Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Nakajima, H., Kotani, D., Bando, H., Kato, T., Oki, E., Shinozaki, E., Sunakawa, Y., Yamazaki, K., Yuki, S., and Nakamura, Y. (2021). REMARRY and PURSUIT Trials: Liquid Biopsy-Guided Rechallenge with Anti-Epidermal Growth Factor Receptor (EGFR) Therapy with Panitumumab plus Irinotecan for Patients with Plasma RAS Wild-Type Metastatic Colorectal Cancer. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08395-2"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"54627","DOI":"10.18632\/oncotarget.10559","article-title":"MET Amplification in Metastatic Colorectal Cancer: An Acquired Response to EGFR Inhibition, Not a de Novo Phenomenon","volume":"7","author":"Raghav","year":"2016","journal-title":"Oncotarget"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"147857","DOI":"10.1016\/j.gene.2023.147857","article-title":"Colorectal Cancer: Genetic Alterations, Novel Biomarkers, Current Therapeutic Strategies and Clinical Trials","volume":"892","author":"Housini","year":"2024","journal-title":"Gene"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Gmeiner, W.H. (2024). Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment. Cancers, 16.","DOI":"10.3390\/cancers16051029"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Patel, A., and Gulhati, P. (2024). Molecular Landscape and Therapeutic Strategies against Colorectal Cancer. Cancers, 16.","DOI":"10.3390\/cancers16081551"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1158\/2326-6066.CIR-23-0189","article-title":"A Bispecific \u0393\u03b4 T-Cell Engager Targeting EGFR Activates a Potent V\u03b39V\u03b42 T Cell\u2013Mediated Immune Response against EGFR-Expressing Tumors","volume":"11","author":"King","year":"2023","journal-title":"Cancer Immunol. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s43018-023-00536-9","article-title":"Precision-Activated T-Cell Engagers Targeting HER2 or EGFR and CD3 Mitigate on-Target, off-Tumor Toxicity for Immunotherapy in Solid Tumors","volume":"4","author":"Cattaruzza","year":"2023","journal-title":"Nat. Cancer"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2315640","DOI":"10.1080\/19420862.2024.2315640","article-title":"Impact of Antibody Architecture and Paratope Valency on Effector Functions of Bispecific NKp30 x EGFR Natural Killer Cell Engagers","volume":"16","author":"Boje","year":"2024","journal-title":"mAbs"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2034355","DOI":"10.1080\/2162402X.2022.2034355","article-title":"Trispecific T-Cell Engagers for Dual Tumor-Targeting of Colorectal Cancer","volume":"11","author":"Harwood","year":"2022","journal-title":"OncoImmunology"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Goulet, D.R., Chatterjee, S., Lee, W.-P., Waight, A.B., Zhu, Y., and Mak, A.N.-S. (2022). Engineering an Enhanced EGFR Engager: Humanization of Cetuximab for Improved Developability. Antibodies, 11.","DOI":"10.3390\/antib11010006"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"100728","DOI":"10.1016\/j.crmeth.2024.100728","article-title":"An Engineering Strategy to Target Activated EGFR with CAR T Cells","volume":"4","author":"Dobersberger","year":"2024","journal-title":"Cell Rep. Methods"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Barros, L.R.C., Couto, S.C.F., Da Silva Santurio, D., Paix\u00e3o, E.A., Cardoso, F., Da Silva, V.J., Klinger, P., Ribeiro, P.D.A.C., R\u00f3s, F.A., and Oliveira, T.G.M. (2022). Systematic Review of Available CAR-T Cell Trials around the World. Cancers, 14.","DOI":"10.3390\/cancers14112667"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Hintzen, G., Dulat, H.J., and Rajkovic, E. (2022). Engaging Innate Immunity for Targeting the Epidermal Growth Factor Receptor: Therapeutic Options Leveraging Innate Immunity versus Adaptive Immunity versus Inhibition of Signaling. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.892212"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12935-021-01763-9","article-title":"Monoclonal Antibodies and Chimeric Antigen Receptor (CAR) T Cells in the Treatment of Colorectal Cancer","volume":"21","author":"Jin","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1146\/annurev-pathmechdis-012419-032611","article-title":"Human Organoids: Tools for Understanding Biology and Treating Diseases","volume":"15","author":"Schutgens","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Goldrick, C., Guri, I., Herrera-Oropeza, G., O\u2019Brien-Gore, C., Roy, E., Wojtynska, M., and Spagnoli, F.M. (2023). 3D Multicellular Systems in Disease Modelling: From Organoids to Organ-on-Chip. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1083175"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-Term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett\u2019s Epithelium","volume":"141","author":"Sato","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3390\/organoids3010003","article-title":"The Next Generation of Organoids Will Be More Complex and Even Closer to Resembling Real Organs: An Interview with Prof. Dr. Hans Clevers","volume":"3","year":"2024","journal-title":"Organoids"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3390\/organoids1010004","article-title":"Organoids, Assembloids and Embryoids: New Avenues for Developmental Biology, Disease Modeling, Drug Testing and Toxicity Assessment without Animal Experimentation","volume":"1","year":"2022","journal-title":"Organoids"},{"key":"ref_170","first-page":"141","article-title":"Drug Resistance and Combating Drug Resistance in Cancer","volume":"2","author":"Wang","year":"2019","journal-title":"Cancer Drug Resist."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/nm.3967","article-title":"The Consensus Molecular Subtypes of Colorectal Cancer","volume":"21","author":"Guinney","year":"2015","journal-title":"Nat. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"8332","DOI":"10.1158\/1078-0432.CCR-05-1030","article-title":"Microsatellite Instability and Colorectal Cancer Prognosis","volume":"11","author":"Benatti","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Greco, L., Rubbino, F., Dal Buono, A., and Laghi, L. (2023). Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability\u2014Lessons from Colorectal Cancer. Genes., 14.","DOI":"10.3390\/genes14061169"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13046-023-02600-9","article-title":"Subtype-Specific Kinase Dependency Regulates Growth and Metastasis of Poor-Prognosis Mesenchymal Colorectal Cancer","volume":"42","author":"Buikhuisen","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.4389","article-title":"Functional Precision Cancer Medicine\u2014Moving beyond Pure Genomics","volume":"23","author":"Letai","year":"2017","journal-title":"Nat. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41698-021-00168-1","article-title":"Patient-Derived Organoids as a Predictive Biomarker for Treatment Response in Cancer Patients","volume":"5","author":"Wensink","year":"2021","journal-title":"NPJ Precis. Oncol."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Su, C., Olsen, K.A., Bond, C.E., and Whitehall, V.L.J. (2023). The Efficacy of Using Patient-Derived Organoids to Predict Treatment Response in Colorectal Cancer. Cancers, 15.","DOI":"10.3390\/cancers15030805"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Kiwaki, T., and Kataoka, H. (2022). Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050695"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"18124","DOI":"10.1038\/s41598-023-45297-8","article-title":"Systematic Review: Predictive Value of Organoids in Colorectal Cancer","volume":"13","author":"Sakshaug","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1038\/s41467-022-30722-9","article-title":"The Drug-Induced Phenotypic Landscape of Colorectal Cancer Organoids","volume":"13","author":"Betge","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"5376","DOI":"10.1158\/1078-0432.CCR-18-3590","article-title":"Patient-Derived Cancer Organoid Cultures to Predict Sensitivity to Chemotherapy and Radiation","volume":"25","author":"Pasch","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.aao2774","article-title":"Patient-Derived Organoids Model Treatment Response of Metastatic Gastrointestinal Cancers","volume":"359","author":"Vlachogiannis","year":"2018","journal-title":"Science"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"eaay2574","DOI":"10.1126\/scitranslmed.aay2574","article-title":"Patient-Derived Organoids Can Predict Response to Chemotherapy in Metastatic Colorectal Cancer Patients","volume":"11","author":"Ooft","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1097\/DCR.0000000000001971","article-title":"Accuracy of Using a Patient-Derived Tumor Organoid Culture Model to Predict the Response to Chemotherapy Regimens In Stage IV Colorectal Cancer: A Blinded Study","volume":"64","author":"Wang","year":"2021","journal-title":"Dis. Colon Rectum"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13046-023-02650-z","article-title":"Platform Combining Statistical Modeling and Patient-Derived Organoids to Facilitate Personalized Treatment of Colorectal Carcinoma","volume":"42","author":"Ramzy","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Costa, D., Ven\u00e8, R., Coco, S., Longo, L., Tosetti, F., Scabini, S., Mastracci, L., Grillo, F., Poggi, A., and Benelli, R. (2023). SB202190 Predicts BRAF-Activating Mutations in Primary Colorectal Cancer Organoids via Erk1-2 Modulation. Cells, 12.","DOI":"10.3390\/cells12040664"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"e005660","DOI":"10.1136\/jitc-2022-005660","article-title":"Targeting of Colorectal Cancer Organoids with Zoledronic Acid Conjugated to the Anti-EGFR Antibody Cetuximab","volume":"10","author":"Benelli","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1136\/gutjnl-2019-320019","article-title":"Organoid Cultures of Early-Onset Colorectal Cancers Reveal Distinct and Rare Genetic Profiles","volume":"69","author":"Yan","year":"2020","journal-title":"Gut"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.stem.2020.04.003","article-title":"Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids","volume":"26","author":"Michels","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"6262","DOI":"10.1016\/j.cell.2021.11.031","article-title":"Differential Pre-Malignant Programs and Microenvironment Chart Distinct Paths to Malignancy in Human Colorectal Polyps","volume":"184","author":"Chen","year":"2021","journal-title":"Cell"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13046-021-01986-8","article-title":"Integrated Multi-Omics Analyses on Patient-Derived CRC Organoids Highlight Altered Molecular Pathways in Colorectal Cancer Progression Involving PTEN","volume":"40","author":"Codrich","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Rathje, F., Klingler, S., and Aberger, F. (2022). Organoids for Modeling (Colorectal) Cancer in a Dish. Cancers, 14.","DOI":"10.3390\/cancers14215416"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.1111\/jcmm.16578","article-title":"Organoid Models of the Tumor Microenvironment and Their Applications","volume":"25","author":"Xia","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"K\u00f6seer, A.S., Di Gaetano, S., Arndt, C., Bachmann, M., and Dubrovska, A. (2023). Immunotargeting of Cancer Stem Cells. Cancers, 15.","DOI":"10.3390\/cancers15051608"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/s41416-018-0118-6","article-title":"Targeting LGR5 in Colorectal Cancer: Therapeutic Gold or Too Plastic?","volume":"118","author":"Morgan","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Sogawa, C., Eguchi, T., Namba, Y., Okusha, Y., Aoyama, E., Ohyama, K., and Okamoto, K. (2021). Gel-Free 3D Tumoroids with Stem Cell Properties Modeling Drug Resistance to Cisplatin and Imatinib in Metastatic Colorectal Cancer. Cells, 10.","DOI":"10.3390\/cells10020344"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1002\/ijc.33226","article-title":"Systems Analysis of Protein Signatures Predicting Cetuximab Responses in KRAS, NRAS, BRAF and PIK3CA Wild-type Patient-derived Xenograft Models of Metastatic Colorectal Cancer","volume":"147","author":"Lindner","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1158\/1535-7163.MCT-22-0415","article-title":"Loss of LGR5 through Therapy-Induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells","volume":"22","author":"Posey","year":"2023","journal-title":"Mol. Cancer Ther."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13073-021-00926-7","article-title":"Secondary Resistance to Anti-EGFR Therapy by Transcriptional Reprogramming in Patient-Derived Colorectal Cancer Models","volume":"13","author":"Vangala","year":"2021","journal-title":"Genome Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1053\/j.gastro.2017.03.053","article-title":"EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients","volume":"153","author":"Srivatsa","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13045-024-01525-w","article-title":"IL-15-Secreting CAR Natural Killer Cells Directed toward the Pan-Cancer Target CD70 Eliminate Both Cancer Cells and Cancer-Associated Fibroblasts","volume":"17","author":"Gehrcken","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12032-021-01464-3","article-title":"Dual Inhibition of TGF\u03b2 and AXL as a Novel Therapy for Human Colorectal Adenocarcinoma with Mesenchymal Phenotype","volume":"38","author":"Ciardiello","year":"2021","journal-title":"Med. Oncol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/procel\/pwad038","article-title":"Drug Repurposing Screening and Mechanism Analysis Based on Human Colorectal Cancer Organoids","volume":"15","author":"Mao","year":"2024","journal-title":"Protein Cell"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1038\/s41467-024-47227-2","article-title":"Membrane to Cortex Attachment Determines Different Mechanical Phenotypes in LGR5+ and LGR5- Colorectal Cancer Cells","volume":"15","author":"Conti","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00018-023-05071-5","article-title":"Inhibition of Autocrine HGF Maturation Overcomes Cetuximab Resistance in Colorectal Cancer","volume":"81","author":"Jones","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.7150\/jca.91089","article-title":"Dual Inhibition of B7-H3 and EGFR Overcomes Acquired Chemoresistance in Colon Adenocarcinoma","volume":"15","author":"Chen","year":"2024","journal-title":"J. Cancer"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/s41416-024-02649-z","article-title":"Inhibition of the AURKA\/YAP1 Axis Is a Promising Therapeutic Option for Overcoming Cetuximab Resistance in Colorectal Cancer Stem Cells","volume":"130","author":"Schlaepfer","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"104005","DOI":"10.1016\/j.drudis.2024.104005","article-title":"AXL Receptor as an Emerging Molecular Target in Colorectal Cancer","volume":"29","author":"Fusco","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41698-024-00543-8","article-title":"A Functional Personalised Oncology Approach against Metastatic Colorectal Cancer in Matched Patient Derived Organoids","volume":"8","author":"Thng","year":"2024","journal-title":"NPJ Precis. Oncol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1038\/s41467-023-38780-3","article-title":"Establishment of Gastrointestinal Assembloids to Study the Interplay between Epithelial Crypts and Their Mesenchymal Niche","volume":"14","author":"Lin","year":"2023","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:07:06Z","timestamp":1760108826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":211,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137131"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137131","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}