Challenges for Triple Negative Breast Cancer Treatment: Defeating Heterogeneity and Cancer Stemness
- PMID: 36077812
- PMCID: PMC9454775
- DOI: 10.3390/cancers14174280
Challenges for Triple Negative Breast Cancer Treatment: Defeating Heterogeneity and Cancer Stemness
Abstract
The Triple Negative Breast Cancer (TNBC) subtype is known to have a more aggressive clinical course compared to other breast cancer subtypes. Targeted therapies for this type of breast cancer are limited and patients are mostly treated with conventional chemo- and radio-therapies which are not specific and do not target resistant cells. Therefore, one of the major clinical challenges is to find compounds that target the drug-resistant cell populations which are responsible for reforming secondary tumours. The molecular profiling of the different TNBC subtypes holds a promise for better defining these resistant cells specific to each tumour. To this end, a better understanding of TNBC heterogeneity and cancer stemness is required, and extensive genomic analysis can help to understand the disease complexity and distinguish new molecular drivers that can be targeted in the clinics. The use of persister cancer cell-targeting therapies combined with other therapies may provide a big advance to improve TNBC patients' survival.
Keywords: differentiation; drug resistance; persister cells; phenotype; stemness; triple negative breast cancer; tumour heterogeneity.
Conflict of interest statement
The authors declare no conflict of interest.
Figures




Similar articles
-
Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer.Cell Oncol (Dordr). 2020 Jun;43(3):431-444. doi: 10.1007/s13402-020-00497-6. Epub 2020 Mar 12. Cell Oncol (Dordr). 2020. PMID: 32166583 Free PMC article.
-
Chemokines in triple-negative breast cancer heterogeneity: New challenges for clinical implications.Semin Cancer Biol. 2022 Nov;86(Pt 2):769-783. doi: 10.1016/j.semcancer.2022.03.008. Epub 2022 Mar 9. Semin Cancer Biol. 2022. PMID: 35278636 Review.
-
Triple negative breast cancer: looking for the missing link between biology and treatments.Oncotarget. 2015 Sep 29;6(29):26560-74. doi: 10.18632/oncotarget.5306. Oncotarget. 2015. PMID: 26387133 Free PMC article. Review.
-
Nucleolar and Coiled-Body Phosphoprotein 1 Is Associated With Stemness and Represents a Potential Therapeutic Target in Triple-Negative Breast Cancer.Front Oncol. 2022 Jan 31;12:731528. doi: 10.3389/fonc.2022.731528. eCollection 2022. Front Oncol. 2022. PMID: 35174077 Free PMC article.
-
YTHDF1 enhances stemness and chemoresistance in triple-negative breast cancer cells by upregulating SIAH2.Mol Carcinog. 2024 Mar;63(3):417-429. doi: 10.1002/mc.23661. Epub 2023 Nov 20. Mol Carcinog. 2024. PMID: 37983722
Cited by
-
Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer.Mol Ther. 2024 Oct 2;32(10):3669-3682. doi: 10.1016/j.ymthe.2024.07.021. Epub 2024 Jul 31. Mol Ther. 2024. PMID: 39086134
-
Human Cytomegalovirus Infection and Breast Cancer: A Literature Review of Clinical and Experimental Data.Biology (Basel). 2025 Feb 8;14(2):174. doi: 10.3390/biology14020174. Biology (Basel). 2025. PMID: 40001942 Free PMC article. Review.
-
A Tumor Microenvironment-Driven Network Regulated by STAT3 and p65 Negatively Controls the Enrichment of Cancer Stem Cells in Human HR+/HER2- Breast Cancer.Cancers (Basel). 2023 Apr 12;15(8):2255. doi: 10.3390/cancers15082255. Cancers (Basel). 2023. PMID: 37190183 Free PMC article.
-
Soft matrix promotes immunosuppression in tumor-resident immune cells via COX-FGF2 signaling.Nat Commun. 2025 May 27;16(1):4908. doi: 10.1038/s41467-025-60092-x. Nat Commun. 2025. PMID: 40425576 Free PMC article.
-
The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation.Sci Rep. 2023 Aug 18;13(1):13456. doi: 10.1038/s41598-023-40669-6. Sci Rep. 2023. PMID: 37596365 Free PMC article.
References
-
- Rakha E.A., Elsheikh S.E., Aleskandarany M.A., Habashi H.O., Green A.R., Powe D.G., El-Sayed M.E., Benhasouna A., Brunet J.S., LAkslen A., et al. Triple-negative breast cancer: Distinguishing between basal and nonbasal subtypes. Clin. Cancer Res. 2009;15:2302–2310. doi: 10.1158/1078-0432.CCR-08-2132. - DOI - PubMed
-
- Goldhirsch A., Winer E.P., Coates A.S., Gelber R.D., Piccart-Gebhart M., Thürlimann B., Senn H.J., Albain K.S., André F., Bergh J., et al. Personalizing the treatment of women with early breast cancer: Highlights of the st gallen international expert consensus on the primary therapy of early breast Cancer 2013. Ann. Oncol. 2013;24:2206–2223. doi: 10.1093/annonc/mdt303. - DOI - PMC - PubMed
-
- Colleoni M., Rotmensz N., Robertson C., Orlando L., Viale G., Renne G., Luini A., Veronesi P., Intra M., Orecchia R., et al. Very young women (<35 years) with operable breast cancer: Features of disease at presentation. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2002;13:273–279. doi: 10.1093/annonc/mdf039. - DOI - PubMed
-
- Morris G.J., Naidu S., Topham A.K., Guiles F., Xu Y., McCue P., Schwartz G.F., Park P.K., Rosenberg A.L., Brill K.L., et al. 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. Cancer. 2007;110:876–884. doi: 10.1002/cncr.22836. - DOI - PubMed
Publication types
Grants and funding
LinkOut - more resources
Full Text Sources