{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:26:23Z","timestamp":1791260783454,"version":"4.1.0"},"reference-count":125,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003327","name":"Cooperative Research Centres, Australian Government Department of Industry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.canlet.2026.218556","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:53:53Z","timestamp":1777762433000},"page":"218556","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Challenges in triple negative breast cancer treatment and therapeutic potential of the mitogen activated protein kinase pathway"],"prefix":"10.1016","volume":"653","author":[{"given":"Prettisha K.","family":"Nand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Croucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3446-0323","authenticated-orcid":false,"given":"Levon M.","family":"Khachigian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2026.218556_bib1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/s41591-025-03502-3","article-title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries","volume":"31","author":"Kim","year":"2025","journal-title":"Nat Med"},{"key":"10.1016\/j.canlet.2026.218556_bib2","author":"Drugs Approved for Breast Cancer","year":"2025","journal-title":"National Cancer Institute"},{"key":"10.1016\/j.canlet.2026.218556_bib3","unstructured":"Types of Breast Cancer, Cancer Australia. www.canceraustralia.gov.au\/cancer-types\/breast-cancer\/types-breast-cancer."},{"key":"10.1016\/j.canlet.2026.218556_bib4","doi-asserted-by":"crossref","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":"10.1016\/j.canlet.2026.218556_bib5","unstructured":"Cancer Stat Facts: Female Breast Cancer Subtypes, National Cancer Institute. https:\/\/seer.cancer.gov\/statfacts\/html\/breast-subtypes.html."},{"key":"10.1016\/j.canlet.2026.218556_bib6","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.3390\/pharmaceutics15071796","article-title":"Triple negative breast cancer treatment options and limitations: future outlook","volume":"15","author":"Obidiro","year":"2023","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.canlet.2026.218556_bib7","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.3390\/cancers12092392","article-title":"Perspectives on triple-negative breast cancer: current treatment strategies, unmet needs, and potential targets for future therapies","volume":"12","author":"Gupta","year":"2020","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.canlet.2026.218556_bib8","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3390\/cells8090957","article-title":"Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge","volume":"8","author":"Nedeljkovic","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.canlet.2026.218556_bib9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-pathol-042420-093238","article-title":"Pathogenesis of triple-negative breast cancer","volume":"17","author":"Derakhshan","year":"2022","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.canlet.2026.218556_bib10","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1172\/JCI45014","article-title":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","volume":"121","author":"Lehmann","year":"2011","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.canlet.2026.218556_bib11","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11070965","article-title":"Targeting cancer stem cells in triple-negative breast cancer","volume":"11","author":"Park","year":"2019","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.canlet.2026.218556_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2024.167164","article-title":"Metabolic adaptations in cancer stem cells: a key to therapy resistance","volume":"1870","author":"Masoudi","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"10.1016\/j.canlet.2026.218556_bib13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41392-024-02108-4","article-title":"Breast cancer: pathogenesis and treatments","volume":"10","author":"Xiong","year":"2025","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.canlet.2026.218556_bib14","unstructured":"Risk Factors for Breast Cancer, Breast Screen NSW, NSW Government. www.breastscreen.nsw.gov.au\/breast-cancer-and-screening\/risk-factors-for-breast-cancer\/."},{"key":"10.1016\/j.canlet.2026.218556_bib15","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/S0140-6736(20)32381-3","article-title":"Breast cancer","volume":"397","author":"Loibl","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.canlet.2026.218556_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2023.115545","article-title":"Triple-Negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies","volume":"212","author":"Karim","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.canlet.2026.218556_bib17","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/cncr.22836","article-title":"Differences in breast carcinoma characteristics in newly diagnosed African-American and caucasian patients: a single-institution compilation compared with the National Cancer Institute's surveillance, epidemiology, and end results database","volume":"110","author":"Morris","year":"2007","journal-title":"Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13578-025-01359-0","article-title":"Classifications of triple-negative breast cancer: insights and current therapeutic approaches","volume":"15","author":"Chen","year":"2025","journal-title":"Cell Biosci."},{"key":"10.1016\/j.canlet.2026.218556_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2024.102993","article-title":"Subtyping of triple-negative breast cancers: its prognostication and implications in diagnosis of breast origin","volume":"9","author":"Hu","year":"2024","journal-title":"ESMO Open"},{"key":"10.1016\/j.canlet.2026.218556_bib20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0157368","article-title":"Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection","volume":"11","author":"Lehmann","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2026.218556_bib21","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/path.4280","article-title":"Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes","volume":"232","author":"Lehmann","year":"2014","journal-title":"J. Pathol."},{"key":"10.1016\/j.canlet.2026.218556_bib22","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1405491","article-title":"Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies","volume":"14","author":"Xiong","year":"2024","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13045-022-01341-0","article-title":"Recent advances in therapeutic strategies for triple-negative breast cancer","volume":"15","author":"Li","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib24","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1158\/1078-0432.CCR-13-0799","article-title":"Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes","volume":"19","author":"Masuda","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib25","doi-asserted-by":"crossref","first-page":"26406","DOI":"10.18632\/oncotarget.25413","article-title":"Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy","volume":"9","author":"Santonja","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2026.218556_bib26","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41422-020-0375-9","article-title":"Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial","volume":"31","author":"Jiang","year":"2021","journal-title":"Cell Res."},{"key":"10.1016\/j.canlet.2026.218556_bib27","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.1002\/jcp.26379","article-title":"Breast cancer diagnosis: imaging techniques and biochemical markers","volume":"233","author":"Jafari","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.canlet.2026.218556_bib28","article-title":"Breast cancer screening for high-risk patients of different ages and risk - which modality is Most effective?","volume":"8","author":"Wellings","year":"2016","journal-title":"Cureus"},{"key":"10.1016\/j.canlet.2026.218556_bib29","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/bjs\/znab145","article-title":"Outcomes after breast-conserving surgery or mastectomy in patients with triple-negative breast cancer: Meta-Analysis","volume":"108","author":"Fancellu","year":"2021","journal-title":"Br. J. Surg."},{"key":"10.1016\/j.canlet.2026.218556_bib30","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.18632\/oncotarget.13976","article-title":"The different outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based Study from the SEER 18 database","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2026.218556_bib31","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13058-020-01296-5","article-title":"Triple-Negative breast cancer molecular subtyping and treatment progress","volume":"22","author":"Yin","year":"2020","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib32","unstructured":"Radiation for Breast Cancer, American Cancer Society. www.cancer.org\/cancer\/types\/breast-cancer\/treatment\/radiation-for-breast-cancer.html."},{"key":"10.1016\/j.canlet.2026.218556_bib33","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1056\/NEJMoa1814213","article-title":"Sacituzumab Govitecan-hziy in refractory metastatic triple-negative breast cancer","volume":"380","author":"Bardia","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib34","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/annonc\/mdy518","article-title":"Pembrolizumab monotherapy for previously untreated, PD-L1-Positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 Study","volume":"30","author":"Adams","year":"2019","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib35","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1056\/NEJMoa2105215","article-title":"Investigators, adjuvant olaparib for patients with BRCA1- or BRCA2-Mutated breast cancer","volume":"384","author":"Tutt","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib36","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1007\/s00432-022-04189-6","article-title":"Triple negative breast cancer: approved treatment options and their mechanisms of action","volume":"149","author":"Mandapati","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib37","first-page":"185","article-title":"Eribulin mesylate as a microtubule inhibitor for treatment of patients with metastatic breast cancer","volume":"4","author":"Munoz-Couselo","year":"2011","journal-title":"OncoTargets Ther."},{"key":"10.1016\/j.canlet.2026.218556_bib38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3892\/or.2023.8612","article-title":"5-Fluorouracil and capecitabine therapies for the treatment of colorectal cancer","volume":"50","author":"Alzahrani","year":"2023","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.canlet.2026.218556_bib39","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.2174\/1871520621666210811105344","article-title":"Alkylating agents, the road less traversed, changing anticancer therapy","volume":"22","author":"Karati","year":"2022","journal-title":"Anti Cancer Agents Med. Chem."},{"key":"10.1016\/j.canlet.2026.218556_bib40","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.molcel.2015.10.032","article-title":"Structural basis of detection and signaling of DNA single-strand breaks by Human PARP-1","volume":"60","author":"Eustermann","year":"2015","journal-title":"Mol Cell"},{"key":"10.1016\/j.canlet.2026.218556_bib41","doi-asserted-by":"crossref","first-page":"7762","DOI":"10.1093\/nar\/gku474","article-title":"PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1","volume":"42","author":"Langelier","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.canlet.2026.218556_bib42","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature03443","article-title":"Specific killing of BRCA2-Deficient tumours with inhibitors of Poly(ADP-ribose) polymerase","volume":"434","author":"Bryant","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2026.218556_bib43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000455999","article-title":"Germline mutations in triple-negative breast cancer","volume":"12","author":"Hahnen","year":"2017","journal-title":"Breast Care"},{"key":"10.1016\/j.canlet.2026.218556_bib44","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1056\/NEJMoa1706450","article-title":"Olaparib for metastatic breast cancer in patients with a germline BRCA mutation","volume":"377","author":"Robson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib45","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.annonc.2020.08.2098","article-title":"Talazoparib versus chemotherapy in patients with germline BRCA1\/2-Mutated HER2-Negative advanced breast cancer: final overall survival results from the EMBRACA trial","volume":"31","author":"Litton","year":"2020","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib46","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1056\/NEJMoa1802905","article-title":"Talazoparib in patients with advanced breast cancer and a germline BRCA mutation","volume":"379","author":"Litton","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib47","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1200\/JCO.2007.14.4147","article-title":"Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer","volume":"26","author":"Liedtke","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib48","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1186\/s12885-022-10076-7","article-title":"Trophoblast cell-surface antigen 2 (TROP2) expression in triple-negative breast cancer","volume":"22","author":"Jeon","year":"2022","journal-title":"BMC Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib49","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1200\/JCO.2016.70.8297","article-title":"Efficacy and safety of Anti-Trop-2 antibody drug Conjugate Sacituzumab Govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer","volume":"35","author":"Bardia","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib50","doi-asserted-by":"crossref","DOI":"10.3390\/cells13242126","article-title":"Targeting refractory triple-negative breast cancer with Sacituzumab Govitecan: a new era in precision medicine","volume":"13","author":"Khan","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.canlet.2026.218556_bib51","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1200\/JCO.23.01409","article-title":"Final results from the randomized phase III ASCENT clinical trial in metastatic triple-negative breast cancer and Association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression","volume":"42","author":"Bardia","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib52","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1200\/JCO.2015.64.8931","article-title":"Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 Study","volume":"34","author":"Nanda","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib53","volume":"7","year":"2017","journal-title":"Cancer Discov."},{"key":"10.1016\/j.canlet.2026.218556_bib54","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/annonc\/mdy517","article-title":"Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study","volume":"30","author":"Adams","year":"2019","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib55","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1056\/NEJMoa1809615","article-title":"Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer","volume":"379","author":"Schmid","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib56","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa1910549","article-title":"Pembrolizumab for early triple-negative breast cancer. Reply","volume":"382","author":"Schmid","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib57","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0140-6736(23)00285-4","article-title":"Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials","volume":"401","author":"Group","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.canlet.2026.218556_bib58","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-005543","article-title":"Anti-TGF-beta\/PD-L1 bispecific antibody promotes T cell infiltration and exhibits enhanced antitumor activity in triple-negative breast cancer","volume":"10","author":"Yi","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib59","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003468","article-title":"Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer","volume":"9","author":"Liu","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib60","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1158\/1078-0432.CCR-22-1601","article-title":"Phase II trial of Pembrolizumab and Anti-CD3 x Anti-HER2 bispecific antibody-armed activated T cells in metastatic castration-resistant prostate cancer","volume":"29","author":"Vaishampayan","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib61","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41392-025-02340-6","article-title":"Epigenetic regulation of cancer stemness","volume":"10","author":"Galassi","year":"2025","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.canlet.2026.218556_bib62","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107205","article-title":"Epigenetic modulations in triple-negative breast cancer: therapeutic implications for tumor microenvironment","volume":"204","author":"Zhou","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.canlet.2026.218556_bib63","doi-asserted-by":"crossref","first-page":"6276","DOI":"10.1038\/s41467-021-26502-6","article-title":"Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes","volume":"12","author":"Lehmann","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2026.218556_bib64","first-page":"422","article-title":"EZH2 promotes migration and invasion of triple-negative breast cancer cells via regulating TIMP2-MMP-2\/-9 pathway","volume":"8","author":"Chien","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib65","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.celrep.2019.12.056","article-title":"Inhibition of EZH2 catalytic activity selectively targets a metastatic subpopulation in triple-negative breast cancer","volume":"30","author":"Yomtoubian","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.canlet.2026.218556_bib66","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252111740","article-title":"Progresses and pitfalls of epigenetics in solid tumors clinical trials","volume":"25","author":"Rossi","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.canlet.2026.218556_bib67","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41571-024-00972-1","article-title":"Getting the right combination to break the epigenetic code","volume":"22","author":"Tolu","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib68","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10549-013-2591-1","article-title":"Clinical-pathologic significance of cancer stem cell marker expression in familial breast cancers","volume":"140","author":"Bane","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.canlet.2026.218556_bib69","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1158\/0008-5472.CAN-05-0626","article-title":"Isolation and in vitro propagation of tumorigenic breast cancer cells with stem\/progenitor cell properties","volume":"65","author":"Ponti","year":"2005","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib70","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nrc1232","article-title":"Applying the principles of stem-cell biology to cancer","volume":"3","author":"Pardal","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib71","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/sj.onc.1210200","article-title":"Targeted therapy for cancer stem cells: the patched pathway and ABC transporters","volume":"26","author":"Lou","year":"2007","journal-title":"Oncogene"},{"key":"10.1016\/j.canlet.2026.218556_bib72","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/jnci\/djn123","article-title":"Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy","volume":"100","author":"Li","year":"2008","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.canlet.2026.218556_bib73","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114673","article-title":"Potassium channels, tumorigenesis and targeted drugs","volume":"162","author":"Xia","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.canlet.2026.218556_bib74","doi-asserted-by":"crossref","DOI":"10.1172\/JCI159839","article-title":"Hypoxia-inducible factors: cancer progression and clinical translation","volume":"132","author":"Wicks","year":"2022","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.canlet.2026.218556_bib75","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1073\/pnas.0530291100","article-title":"Prospective identification of tumorigenic breast cancer cells","volume":"100","author":"Al-Hajj","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.canlet.2026.218556_bib76","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.stem.2018.12.009","article-title":"The architects of the tumor ecosystem","volume":"24","author":"Prager","year":"2019","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.canlet.2026.218556_bib77","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.semcancer.2021.06.015","article-title":"Cancer stem cells in TNBC","volume":"82","author":"Hua","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.canlet.2026.218556_bib78","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.stemcr.2013.11.009","article-title":"Breast cancer stem cells transition between epithelial and mesenchymal States reflective of their normal counterparts","volume":"2","author":"Liu","year":"2014","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.canlet.2026.218556_bib79","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1158\/1535-7163.MCT-15-0243","article-title":"MEK inhibitor selumetinib (AZD6244; ARRY-142886) prevents lung metastasis in a triple-negative breast cancer Xenograft model","volume":"14","author":"Bartholomeusz","year":"2015","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.canlet.2026.218556_bib80","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-Mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.canlet.2026.218556_bib81","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/bies.1132","article-title":"Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition","volume":"23","author":"Savagner","year":"2001","journal-title":"Bioessays"},{"key":"10.1016\/j.canlet.2026.218556_bib82","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.689839","article-title":"A systematic review to clarify the prognostic values of CD44 and CD44(+)CD24(-) phenotype in triple-negative breast cancer patients: lessons learned and the road ahead","volume":"11","author":"Abdoli Shadbad","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib83","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.3390\/curroncol31060232","article-title":"Immunotherapeutic strategies targeting breast cancer stem cells","volume":"31","author":"Vasileiou","year":"2024","journal-title":"Curr. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.105320","article-title":"Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications","volume":"163","author":"Zeng","year":"2021","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.canlet.2026.218556_bib85","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib86","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a011254","article-title":"MAP kinase pathways","volume":"4","author":"Morrison","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"10.1016\/j.canlet.2026.218556_bib87","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11030735","article-title":"Identification of kinase targets for enhancing the Antitumor activity of eribulin in triple-negative breast cell lines","volume":"11","author":"Xie","year":"2023","journal-title":"Biomedicines"},{"key":"10.1016\/j.canlet.2026.218556_bib88","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/jnci\/djab128","article-title":"Identification of the JNK-Active triple-negative breast cancer cluster associated with an immunosuppressive tumor microenvironment","volume":"114","author":"Semba","year":"2022","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.canlet.2026.218556_bib89","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s41467-020-15188-x","article-title":"Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs","volume":"11","author":"Pein","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2026.218556_bib90","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.3892\/or.2017.5452","article-title":"Upregulation of p38 pathway accelerates proliferation and migration of MDA-MB-231 breast cancer cells","volume":"37","author":"Huth","year":"2017","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.canlet.2026.218556_bib91","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s10549-013-2498-x","article-title":"EZH2 inhibition decreases p38 signaling and suppresses breast cancer motility and metastasis","volume":"138","author":"Moore","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.canlet.2026.218556_bib92","article-title":"Deubiquitinating enzyme USP42 promotes breast cancer progression by inhibiting JNK\/p38-mediated apoptosis","volume":"15","author":"He","year":"2025","journal-title":"Sci. Rep."},{"key":"10.1016\/j.canlet.2026.218556_bib93","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/ijc.28958","article-title":"p38 MAPK inhibits breast cancer metastasis through regulation of stromal expansion","volume":"136","author":"Hong","year":"2015","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib94","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012469","article-title":"Role of JNK in a Trp53-dependent mouse model of breast cancer","volume":"5","author":"Cellurale","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2026.218556_bib95","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.36389","article-title":"The cJUN NH(2)-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation","volume":"7","author":"Girnius","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.canlet.2026.218556_bib96","first-page":"275","article-title":"Rationale for targeting the Ras\/MAPK pathway in triple-negative breast cancer","volume":"17","author":"Giltnane","year":"2014","journal-title":"Discov. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib97","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1158\/1541-7786.MCR-20-0687","article-title":"The MEK\/ERK network as a therapeutic target in human cancer","volume":"19","author":"Barbosa","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib98","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.3390\/ijms23031464","article-title":"MAPK\/ERK pathway as a central regulator in vertebrate organ regeneration","volume":"23","author":"Wen","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.canlet.2026.218556_bib99","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1158\/2767-9764.CRC-24-0255","article-title":"Targeting the epidermal growth factor receptor pathway in chemotherapy-resistant triple-negative breast cancer: a phase II Study","volume":"4","author":"Yam","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"10.1016\/j.canlet.2026.218556_bib100","first-page":"1842","article-title":"Expression and clinical significance of MAPK and EGFR in triple-negative breast cancer","volume":"19","author":"Jiang","year":"2020","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.canlet.2026.218556_bib101","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/nm.2795","article-title":"Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance","volume":"18","author":"Balko","year":"2012","journal-title":"Nat Med"},{"key":"10.1016\/j.canlet.2026.218556_bib102","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1158\/0008-5472.CAN-08-3389","article-title":"Basal subtype and MAPK\/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition","volume":"69","author":"Mirzoeva","year":"2009","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib103","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0002888","article-title":"Generation of breast cancer stem cells through epithelial-mesenchymal transition","volume":"3","author":"Morel","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2026.218556_bib104","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10549-019-05166-3","article-title":"Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer","volume":"175","author":"Lee","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.canlet.2026.218556_bib105","doi-asserted-by":"crossref","first-page":"4940","DOI":"10.3390\/ijms22094940","article-title":"Activated ERK signaling is one of the major hub signals related to the acquisition of radiotherapy-resistant MDA-MB-231 breast cancer cells","volume":"22","author":"Paramanantham","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.canlet.2026.218556_bib106","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s10549-017-4440-0","article-title":"Metalloprotease-Dependent activation of EGFR modulates CD44(+)\/CD24(-) populations in triple negative breast cancer cells through the MEK\/ERK pathway","volume":"166","author":"Wise","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.canlet.2026.218556_bib107","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.canlet.2026.218556_bib108","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035826","article-title":"Receptor tyrosine kinases activate canonical WNT\/beta-catenin signaling via MAP kinase\/LRP6 pathway and direct beta-catenin phosphorylation","volume":"7","author":"Krejci","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2026.218556_bib109","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.biopha.2018.09.067","article-title":"PMA treated THP-1-derived-IL-6 promotes EMT of SW48 through STAT3\/ERK-dependent activation of Wnt\/beta-catenin signaling pathway","volume":"108","author":"Gao","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.canlet.2026.218556_bib110","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0085502","article-title":"The MEK\/ERK pathway promotes NOTCH signalling in pancreatic cancer cells","volume":"8","author":"Tremblay","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2026.218556_bib111","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/0008-5472.CAN-08-2331","article-title":"Epidermal growth factor receptor signaling synergizes with Hedgehog\/GLI in oncogenic transformation via activation of the MEK\/ERK\/JUN pathway","volume":"69","author":"Schnidar","year":"2009","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib112","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.biocel.2010.04.016","article-title":"Activation of Erk by sonic hedgehog independent of canonical hedgehog signalling","volume":"42","author":"Chang","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.canlet.2026.218556_bib113","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.semcancer.2015.08.003","article-title":"Mitogen-activated protein kinases and Hedgehog-GLI signaling in cancer: a crosstalk providing therapeutic opportunities?","volume":"35","author":"Rovida","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.canlet.2026.218556_bib114","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10549-024-07551-z","article-title":"Phase II Study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795\/Uprosertib in patients with metastatic triple negative breast cancer","volume":"210","author":"Prasath","year":"2025","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.canlet.2026.218556_bib115","doi-asserted-by":"crossref","first-page":"415","DOI":"10.20892\/j.issn.2095-3941.2019.0137","article-title":"Synergistic inhibition of MEK and reciprocal feedback networks for targeted intervention in malignancy","volume":"16","author":"Li","year":"2019","journal-title":"Cancer Biol. Med."},{"key":"10.1016\/j.canlet.2026.218556_bib116","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abp8314","article-title":"Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma","volume":"9","author":"Hastings","year":"2023","journal-title":"Sci. Adv."},{"key":"10.1016\/j.canlet.2026.218556_bib117","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aab0990","article-title":"Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients","volume":"8","author":"Fey","year":"2015","journal-title":"Sci. Signal."},{"key":"10.1016\/j.canlet.2026.218556_bib118","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/msb.2011.27","article-title":"Strong negative feedback from Erk to Raf confers robustness to MAPK signalling","volume":"7","author":"Fritsche-Guenther","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"10.1016\/j.canlet.2026.218556_bib119","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.7150\/jca.13266","article-title":"Comprehensive Two- and three-dimensional RNAi screening identifies PI3K inhibition as a complement to MEK inhibitor AS703026 for combination treatment of triple-negative breast cancer","volume":"6","author":"Lee","year":"2015","journal-title":"J. Cancer"},{"key":"10.1016\/j.canlet.2026.218556_bib120","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1158\/2767-9764.CRC-25-0428","article-title":"A phase IB Study of binimetinib and palbociclib in molecularly selected advanced triple-negative breast cancer","volume":"5","author":"Manso","year":"2025","journal-title":"Cancer Res. Commun."},{"key":"10.1016\/j.canlet.2026.218556_bib121","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1158\/1078-0432.CCR-15-1125","article-title":"RAS\/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1\/PD-L1 immune checkpoint inhibitors","volume":"22","author":"Loi","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib122","first-page":"603","article-title":"MEK inhibition activates STAT signaling to increase breast cancer immunogenicity via MHC-I expression","volume":"3","author":"Franklin","year":"2020","journal-title":"Cancer Drug Resist"},{"key":"10.1016\/j.canlet.2026.218556_bib123","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1007\/s00432-021-03694-4","article-title":"Inhibitors of PD-1\/PD-L1 and ERK1\/2 impede the proliferation of receptor positive and triple-negative breast cancer cell lines","volume":"147","author":"Brautigam","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218556_bib124","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1158\/1078-0432.CCR-24-3001","article-title":"Pembrolizumab in combination with binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer","volume":"31","author":"Chumsri","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218556_bib125","doi-asserted-by":"crossref","DOI":"10.3390\/biom13101480","article-title":"Combination treatment strategies to overcome PARP inhibitor resistance","volume":"13","author":"Soung","year":"2023","journal-title":"Biomolecules"}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526003198?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526003198?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T20:42:41Z","timestamp":1780951361000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383526003198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":125,"alternative-id":["S0304383526003198"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218556","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Challenges in triple negative breast cancer treatment and therapeutic potential of the mitogen activated protein kinase pathway","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218556","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"218556"}}