Therapeutic options for triple-negative breast cancers with defective homologous recombination |
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Authors: | Janneke E. Jaspers Sven Rottenberg Jos Jonkers |
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Affiliation: | Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands |
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Abstract: | Breast cancer is the most common malignancy among women in developed countries, affecting more than a million women per year worldwide. Over the last decades, our increasing understanding of breast cancer biology has led to the development of endocrine agents against hormone receptor-positive tumors and targeted therapeutics against HER2-expressing tumors. However, no targeted therapy is available for patients with triple-negative breast cancer, lacking expression of hormone receptors and HER2. Overlap between BRCA1-mutated breast cancers and triple-negative tumors suggests that an important part of the triple-negative tumors may respond to therapeutics targeting BRCA1-deficient cells. Here, we review the features shared between triple-negative, basal-like and BRCA1-related breast cancers. We also discuss the development of novel therapeutic strategies to target BRCA1-mutated tumors and triple-negative tumors with BRCA1-like features. Finally, we highlight the utility of mouse models for BRCA1-mutated breast cancer to optimize (combination) therapy and to understand drug resistance. |
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Keywords: | ABC, ATP-binding cassette APC, Adenomatous, polyposis coli ATM, Ataxia telangiectasia mutated ATR, ATM and Rad3-related BER, base-excision repair BRCA1, Breast cancer susceptibility gene 1 BRCA2, Breast cancer susceptibility gene 2 CGH, Comparative genomic hybridization CK, Cytokeratin CNA, Copy number alteration CSC, Cancer stem cell DSB, Double strand break EGFR, Epidermal growth factor receptor ER, Estrogen receptor FA, Fanconi anemia Fz, Frizzled FFPE, Formalin-fixed paraffin-embedded GEM, Genetically engineered mouse GSI, γ-secretase inhibitor HDR, Homology-directed repair HER1, Heregulin 1 HER2, Heregulin 2 HH, Hedgehog HR, Homologous recombination ICL, Interstrand cross link ID4, Inhibitor of differentiation 4 IR, Ionizing radiation LOH, Loss of heterozygosity MDR, Multidrug resistance MRN, Mre11/RAD50/NBS1 MRP, Multidrug resistance-associated protein NHEJ, Non-homologous end joining ORF, Open reading frame PALB2, Partner and localizer of BRCA2 PAR, Poly (ADP-ribose) PARP, Poly (ADP-ribose) polymerase PARPi, PARP inhibitor PDGFRv, Platelet-derived growth factor receptor P-gp, P-glycoprotein PR, Progesterone receptor RTV, Relative tumor volume PTCH, Patched SCF, Stem cell factor SERM, Selective estrogen receptor modulator siRNA, Small interfering RNA SMO, Smoothened SSB, Single strand break TIC, Tumor-initiating cell TMA, Tissue microarray TNBC, Triple-negative breast cancer |
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