{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:16:12Z","timestamp":1785406572450,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/6-099-01\/503-61-001"],"award-info":[{"award-number":["503\/6-099-01\/503-61-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"award":["503\/6-099-01\/503-61-001"],"award-info":[{"award-number":["503\/6-099-01\/503-61-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>More than 20 years after the discovery of lunasin, a clear shift in lunasin research is observable\u2014from an initial focus on its direct in vitro anticancer effects toward strategies aimed at improving its bioavailability and repositioning it as a potential adjunct in cancer therapy. Lunasin, a soy-derived bioactive peptide, has been extensively studied for its antineoplastic properties. However, its limited oral bioavailability restrains its efficacy in clinical trials. Therefore, recent research on lunasin points towards the possibility of using it as an adjunct in cancer treatment, rather than as a stand-alone nutraceutical in humans. In preclinical models, in vitro and in vivo, lunasin can enhance the effects of standard anticancer drugs in breast and colon cancers. Research suggests that lunasin can potentiate the effects of drugs, such as tamoxifen, aspirin, cisplatin, and oxaliplatin, by sensitizing cancer cells to apoptosis, modulating cell cycle progression, reducing metastatic potential, and attenuating drug-resistance pathways, including PI3K\/Akt, FAK\/MAPK1\/NF-\u03baB, and integrin-mediated signaling. In combination with those drugs, lunasin exerts significant anticancer effects at concentrations substantially lower than those proven as effective in monotherapy, suggesting a potential role in dose reduction in conventional agents and, subsequently, mitigation of their adverse effects. Although the enhanced effect of those combinations has been shown in preclinical models, there is a distinct lack of human clinical trials in this matter. Available evidence supports a promising concept of lunasin as a molecular \u201cpriming\u201d agent that might complement cytotoxic therapies rather than replace them. This combination-oriented paradigm may represent a shift in lunasin research and offer a novel direction for the use of bioactive peptides in precision oncology; however, further studies exploring this possibility, including human clinical trials, are needed to elucidate lunasin\u2019s role in nutraceutical-assisted cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms27136079","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:53:46Z","timestamp":1783418026000},"page":"6079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Co-Exposure to Lunasin and Other Drugs as a Potential Chemopreventive Strategy Against Breast and Colon Cancers: A Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Aleksandra","family":"Janiak","sequence":"first","affiliation":[{"name":"Department of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-7280","authenticated-orcid":false,"given":"Agnieszka","family":"Kaufman-Szymczyk","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-0922","authenticated-orcid":false,"given":"Katarzyna","family":"Lubecka-Gajewska","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106535","DOI":"10.1016\/j.intimp.2020.106535","article-title":"Breast Cancer: Biology, Biomarkers, and Treatments","volume":"84","author":"Barzaman","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Sancha, N., Corchado-Cobos, R., and P\u00e9rez-Losada, J. (2025). Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26072993"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Papa, A., and Pandolfi, P.P. (2019). The PTEN\u2013PI3K Axis in Cancer. Biomolecules, 9.","DOI":"10.20944\/preprints201904.0127.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000543921","article-title":"Colorectal Cancer: Epidemiology, Risk Factors, and Public Health Strategies","volume":"106","author":"Matsuda","year":"2025","journal-title":"Digestion"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Delle Cave, D. (2025). Advances in Molecular Mechanisms and Therapeutic Strategies in Colorectal Cancer: A New Era of Precision Medicine. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010346"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.canlet.2010.02.010","article-title":"Lunasin Promotes Apoptosis in Human Colon Cancer Cells by Mitochondrial Pathway Activation and Induction of Nuclear Clusterin Expression","volume":"295","author":"Dia","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_8","first-page":"7473","article-title":"Chemopreventive Property of a Soybean Peptide (Lunasin) That Binds to Deacetylated Histones and Inhibits Acetylation","volume":"61","author":"Galvez","year":"2001","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1002\/mnfr.201000632","article-title":"Relationship between Lunasin\u2019s Sequence and Its Inhibitory Activity of Histones H3 and H4 Acetylation","volume":"55","author":"Hsieh","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.3892\/ol.2017.6017","article-title":"Lunasin: A Promising Polypeptide for the Prevention and Treatment of Cancer","volume":"13","author":"Wan","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Alves de Souza, S.M., Hern\u00e1ndez-Ledesma, B., and de Souza, T.L.F. (2022). Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179548"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8991","DOI":"10.29219\/fnr.v67.8991","article-title":"Seed-Derived Peptide Lunasin Suppressed Breast Cancer Cell Growth by Regulating Inflammatory Mediators, Aromatase, and Estrogen Receptors","volume":"67","author":"Hsieh","year":"2023","journal-title":"Food Nutr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12263-012-0307-5","article-title":"The Soybean Peptide Lunasin Promotes Apoptosis of Mammary Epithelial Cells via Induction of Tumor Suppressor PTEN: Similarities and Distinct Actions from Soy Isoflavone Genistein","volume":"8","author":"Pabona","year":"2013","journal-title":"Genes Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3892\/or.2016.4798","article-title":"Lunasin Suppresses the Migration and Invasion of Breast Cancer Cells by Inhibiting Matrix Metalloproteinase-2\/-9 via the FAK\/Akt\/ERK and NF-\u03baB Signaling Pathways","volume":"36","author":"Jiang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/mnfr.201000419","article-title":"Lunasin Induces Apoptosis and Modifies the Expression of Genes Associated with Extracellular Matrix and Cell Adhesion in Human Metastatic Colon Cancer Cells","volume":"55","author":"Dia","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Tom\u00e9, S., Xu, F., Han, Y., Hern\u00e1ndez-Ledesma, B., and Xiao, H. (2020). Inhibitory Effects of Peptide Lunasin in Colorectal Cancer HCT-116 Cells and Their Tumorsphere-Derived Subpopulation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020537"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4236\/jct.2013.46A2005","article-title":"De Potential of Lunasin Orally-Administered in Comparison to Intraperitoneal Injection to Inhibit Colon Cancer Metastasis in Vivo","volume":"4","author":"Dia","year":"2013","journal-title":"J. Cancer Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hsieh, C.-C., Hern\u00e1ndez-Ledesma, B., Jeong, H.J., Park, J.H., and Lumen, B.O. (2010). De Complementary Roles in Cancer Prevention: Protease Inhibitor Makes the Cancer Preventive Peptide Lunasin Bioavailable. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008890"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/19390211.2019.1577937","article-title":"The Effect of Soybean Lunasin on Cardiometabolic Risk Factors: A Randomized Clinical Trial","volume":"17","author":"Haddad","year":"2020","journal-title":"J. Diet. Suppl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/21678421.2018.1556698","article-title":"Lunasin Does Not Slow ALS Progression: Results of an Open-Label, Single-Center, Hybrid-Virtual 12-Month Trial","volume":"20","author":"Bedlack","year":"2019","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1021\/jf803303k","article-title":"Presence of Lunasin in Plasma of Men after Soy Protein Consumption","volume":"57","author":"Dia","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"nzaa045_033","DOI":"10.1093\/cdn\/nzaa045_033","article-title":"The Presence of Lunasin, a Soy-Derived Bioactive Peptide in Plasma: A Randomized Clinical Trial","volume":"4","author":"Tabrizi","year":"2020","journal-title":"Curr. Dev. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.32768\/abc.2025122203-210","article-title":"Soybean Extract Rich in Lunasin Enhances P21 Expression in DMBA-Induced Breast Cancer Rat: A Potential Adjuvant Therapy: Unasin Enhances P21 in Breast Cancer","volume":"12","author":"Evita","year":"2025","journal-title":"Arch. Breast Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"902","DOI":"10.12688\/f1000research.55385.1","article-title":"The Potential of Lunasin Extract for the Prevention of Breast Cancer Progression by Upregulating E-Cadherin and Inhibiting ICAM-1","volume":"10","author":"Kusmardi","year":"2021","journal-title":"F1000Research"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.canlet.2011.09.002","article-title":"Lunasin Potentiates the Effect of Oxaliplatin Preventing Outgrowth of Colon Cancer Metastasis, Binds to A5\u03b21 Integrin and Suppresses FAK\/ERK\/NF-\u03baB Signaling","volume":"313","author":"Dia","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11130-011-0229-1","article-title":"Lunasin\u2013Aspirin Combination Against NIH\/3T3 Cells Transformation Induced by Chemical Carcinogens","volume":"66","author":"Hsieh","year":"2011","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cbi.2010.04.027","article-title":"Lunasin, a Novel Seed Peptide, Sensitizes Human Breast Cancer MDA-MB-231 Cells to Aspirin-Arrested Cell Cycle and Induced Apoptosis","volume":"186","author":"Hsieh","year":"2010","journal-title":"Chem.-Biol. Interact."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mansouri, H., Irchad, A., Rubaka, C., Kisula, L., Hamza, A.A., and Sauli, E. (2026). Botanical Adjuvants in Oncology: A Review on Natural Compounds in Synergy with Conventional Therapies as Next-Generation Enhancers of Breast Cancer Treatment. Curr. Issues Mol. Biol., 48.","DOI":"10.3390\/cimb48020170"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s40001-024-01856-x","article-title":"Homoharringtonine: Updated Insights into Its Efficacy in Hematological Malignancies, Diverse Cancers and Other Biomedical Applications","volume":"29","author":"Khatua","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_30","first-page":"2070","article-title":"Lunasin as a Promising Health-Beneficial Peptide","volume":"18","author":"Liu","year":"2014","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_31","unstructured":"(2026, March 20). Sequence 1 from Patent US 9066906\u2013Protein\u2013NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/protein\/AMF28072.1?report=graph."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.foodchem.2012.09.101","article-title":"Structural Property of Soybean Lunasin and Development of a Method to Quantify Lunasin in Plasma Using an Optimized Immunoassay Protocol","volume":"138","author":"Dia","year":"2013","journal-title":"Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"133933","DOI":"10.1016\/j.ijbiomac.2024.133933","article-title":"\u201cTop-down\u201d Overexpression Optimization of Butelase-1 in Escherichia Coli and Its Application in Anti-Tumor Peptides","volume":"276","author":"Zhao","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Locklear, R., Kusumah, J., Rashad, L., Lugaro, F., Viera, S., Kipyego, N., Kipkosgei, F., Jerop, D., Jacquet, S., and Kassem, M.A. (2025). Multi-Locus GWAS Mapping and Candidate Gene Analysis of Anticancer Peptide Lunasin in Soybean (Glycine Max L. Merr.). Plants, 14.","DOI":"10.3390\/plants14142169"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5882","DOI":"10.1021\/jf0496752","article-title":"Lunasin Concentration in Different Soybean Genotypes, Commercial Soy Protein, and Isoflavone Products","volume":"52","author":"Nelson","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"106370","DOI":"10.1016\/j.fbio.2025.106370","article-title":"Lunasin, Soluble Protein Concentration and Profile in Glycine Soja Compared to Glycine Max, Bioaccessibility and Peptides Bioactivity","volume":"68","author":"Kusumah","year":"2025","journal-title":"Food Biosci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-L\u00f3pez, J.O., Casta\u00f1eda-Reyes, E.D., and D\u00e1vila-Ortiz, G. (2025). Lunasin-like Peptide in Legume and Cereal Seeds: A Review. Int. J. Environ. Res. Public Health, 22.","DOI":"10.3390\/ijerph22101505"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103726","DOI":"10.1016\/j.fbio.2024.103726","article-title":"Functional Exploration of Lunasin Peptide in Transgenic Maize (Zea Mays L.) and Its Role in Controlling Mitophagy in MDA-MB-231 Cells","volume":"58","author":"Hao","year":"2024","journal-title":"Food Biosci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fan, X., Qin, P., Hao, Y., Guo, H., Blecker, C., Everaert, N., and Ren, G. (2020). Overexpression of Soybean-Derived Lunasin in Wheat and Assessment of Its Anti-Proliferative Activity in Colorectal Cancer HT-29 Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249594"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/mnfr.200900073","article-title":"Lunasin, with an arginine\u2013glycine\u2013aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3","volume":"54","author":"Wang","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1039\/C5FO00454C","article-title":"The Protective Role of the Bowman-Birk Protease Inhibitor in Soybean Lunasin Digestion: The Effect of Released Peptides on Colon Cancer Growth","volume":"6","author":"Arques","year":"2015","journal-title":"Food Funct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jfca.2017.01.011","article-title":"Transepithelial Transport of Lunasin and Derived Peptides: Inhibitory Effects on the Gastrointestinal Cancer Cells Viability","volume":"68","author":"Recio","year":"2018","journal-title":"J. Food Compos. Anal."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cam, A., Sivaguru, M., and Gonzalez de Mejia, E. (2013). Endocytic Mechanism of Internalization of Dietary Peptide Lunasin into Macrophages in Inflammatory Condition Associated with Cardiovascular Disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072115"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1093\/jaoac\/91.4.932","article-title":"Lunasin: A Novel Cancer Preventive Seed Peptide That Modifies Chromatin","volume":"91","year":"2008","journal-title":"J. AOAC Int."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Klojdov\u00e1, I., Milota, T., Smetanov\u00e1, J., and Stathopoulos, C. (2023). Encapsulation: A Strategy to Deliver Therapeutics and Bioactive Compounds?. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030362"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Casta\u00f1eda-Reyes, E.D., Gonzalez de Mejia, E., Eller, F.J., Berhow, M.A., Perea-Flores, M.d.J., and D\u00e1vila-Ort\u00edz, G. (2021). Liposomes Loaded with Unsaponifiable Matter from Amaranthus Hypochondriacus as a Source of Squalene and Carrying Soybean Lunasin Inhibited Melanoma Cells. Nanomaterials, 11.","DOI":"10.3390\/nano11081960"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"27858","DOI":"10.1038\/s41598-024-79448-2","article-title":"Encapsulation of Soybean Lunasin and Amaranth Unsaponifiable Matter in Liposomes Induces Cell Cycle Arrest in an Allograft Melanoma Mouse Model","volume":"14","author":"Yahya","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Casta\u00f1eda-Reyes, E.D., Perea-Flores, M.d.J., D\u00e1vila-Ortiz, G., and Gonzalez de Mejia, E. (2022). Liposomes Loaded with Amaranth Unsaponifiable Matter and Soybean Lunasin Prevented Melanoma Tumor Development Overexpressing Caspase-3 in an In Vivo Model. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102214"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"D\u00e1vila-Ortiz, G., Casta\u00f1eda-Reyes, E.D., Ju\u00e1rez-Palomo, C.I., Perea-Flores, M.d.J., P\u00e9rez-Past\u00e9n-Borja, R., M\u00e1rquez-Flores, Y.K., and Gonz\u00e1lez de Mej\u00eda, E. (2022). Liposomes Containing Amaranth Unsaponifiable Matter and Soybean Lunasin Suppress ROS Production in Fibroblasts and Reduced Interleukin Production in Macrophages. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph191811678"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.peptides.2008.11.002","article-title":"Lunasin, a Novel Seed Peptide for Cancer Prevention","volume":"30","author":"Hsieh","year":"2009","journal-title":"Peptides"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.18632\/oncotarget.3080","article-title":"The Soybean-Derived Peptide Lunasin Inhibits Non-Small Cell Lung Cancer Cell Proliferation by Suppressing Phosphorylation of the Retinoblastoma Protein","volume":"6","author":"McConnell","year":"2014","journal-title":"Oncotarget"},{"key":"ref_52","unstructured":"(2026, March 24). Cancer Today. Available online: https:\/\/gco.iarc.who.int\/today\/."},{"key":"ref_53","first-page":"13","article-title":"Diet and Risk of Breast Cancer","volume":"20","author":"Kotepui","year":"2016","journal-title":"Contemp. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41467-024-55219-5","article-title":"Diet-Wide Analyses for Risk of Colorectal Cancer: Prospective Study of 12,251 Incident Cases among 542,778 Women in the UK","volume":"16","author":"Papier","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_55","unstructured":"Gold, J.M., and Raja, A. (2026). Cisplatin. StatPearls, StatPearls Publishing."},{"key":"ref_56","unstructured":"Devanabanda, B., and Kasi, A. (2026). Oxaliplatin. StatPearls, StatPearls Publishing."},{"key":"ref_57","unstructured":"Patel, P., and Jacobs, T.F. (2026). Tamoxifen. StatPearls, StatPearls Publishing."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12943-024-02150-4","article-title":"Tumor-Intrinsic Role of ICAM-1 in Driving Metastatic Progression of Triple-Negative Breast Cancer through Direct Interaction with EGFR","volume":"23","author":"Kang","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"K\u00f6berle, B., and Schoch, S. (2021). Platinum Complexes in Colorectal Cancer and Other Solid Tumors. Cancers, 13.","DOI":"10.3390\/cancers13092073"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"611","DOI":"10.18632\/aging.102644","article-title":"Aspirin Enhances the Sensitivity of Colon Cancer Cells to Cisplatin by Abrogating the Binding of NF-\u03baB to the COX-2 Promoter","volume":"12","author":"Jiang","year":"2020","journal-title":"Aging"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ye, T., Wu, C., Na, J., Liu, X., and Huang, Y. (2025). Multi-Pathway Study for Oxaliplatin Resistance Reduction. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47030172"},{"key":"ref_63","first-page":"12","article-title":"Intraperitoneal Route of Drug Administration: Should It Be Used in Experimental Animal Studies?","volume":"37","author":"Archie","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41416-023-02158-5","article-title":"Tamoxifen Evolution","volume":"128","author":"Howell","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yao, J., Deng, K., Huang, J., Zeng, R., and Zuo, J. (2020). Progress in the Understanding of the Mechanism of Tamoxifen Resistance in Breast Cancer. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.592912"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bcp.2010.03.033","article-title":"Functional Characterization of Gefitinib Uptake in Non-Small Cell Lung Cancer Cell Lines","volume":"80","author":"Galetti","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1517\/14740338.5.3.469","article-title":"Gefitinib: An Adverse Effects Profile","volume":"5","author":"Cersosimo","year":"2006","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Nedeljkovi\u0107, M., and Damjanovi\u0107, A. (2019). Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer\u2014How We Can Rise to the Challenge. Cells, 8.","DOI":"10.3390\/cells8090957"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Presti, D., and Quaquarini, E. (2019). The PI3K\/AKT\/mTOR and CDK4\/6 Pathways in Endocrine Resistant HR+\/HER2\u2212 Metastatic Breast Cancer: Biological Mechanisms and New Treatments. Cancers, 11.","DOI":"10.3390\/cancers11091242"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"112000","DOI":"10.1016\/j.ejrad.2025.112000","article-title":"Colon Cancer Biology and Treatment in the Era of Precision Oncology: A Primer for Radiologists","volume":"185","author":"Platt","year":"2025","journal-title":"Eur. J. Radiol."},{"key":"ref_71","first-page":"1","article-title":"Platinum Accumulation in Chemotherapy: Toxicity Mechanisms, Challenges, and Mitigation Strategies","volume":"51","author":"Lai","year":"2026","journal-title":"Biometals"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.3748\/wjg.v9.i12.2863","article-title":"Expression of PCNA and CD44mRNA in Colorectal Cancer with Venous Invasion and Its Relationship to Liver Metastasis","volume":"9","author":"Yue","year":"2003","journal-title":"World J. Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.3390\/ijms16035386","article-title":"Different Apoptotic Pathways Activated by Oxaliplatin in Primary Astrocytes vs. Colo-Rectal Cancer Cells","volume":"16","author":"Zanardelli","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Saber, M.M., Al-mahallawi, A.M., Nassar, N.N., Stork, B., and Shouman, S.A. (2018). Targeting Colorectal Cancer Cell Metabolism through Development of Cisplatin and Metformin Nano-Cubosomes. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4727-5"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e40380","DOI":"10.1097\/MD.0000000000040380","article-title":"Homoharringtonine in the Treatment of Acute Myeloid Leukemia: A Review","volume":"103","author":"Shen","year":"2024","journal-title":"Medicine"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6079\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:59:27Z","timestamp":1783418367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":75,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27136079"],"URL":"https:\/\/doi.org\/10.3390\/ijms27136079","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]}}}