Synthetic lethal approaches to breast cancer therapy.
The promise of personalized therapy for breast cancer is that therapeutic efficacy will be increased while toxic effects are reduced to a minimum. To achieve this goal, there is now an emphasis on the design of therapies that are based not only on the clinical manifestations of the disease, but also on the underlying molecular and cellular biology of cancer. However, identifying targets for personalized therapies in breast cancer is challenging. Here, we describe how biological concepts such as synthetic lethality and oncogene addiction can be used to identify new therapeutic targets and approaches. We discuss the current clinical developments in implementing synthetic lethality therapies, and highlight new ways in which this approach could be used to target specific subsets of breast cancer.
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Farah L
FL
Rehman
Christopher J
CJ
Lord
Alan
A
Ashworth
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000172:deficiency / Q000502:physiology; D024682:BRCA2 Protein / Q000172:deficiency / Q000502:physiology; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019090:Case Management; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009154:Mutation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D057285:Precision Medicine / Q000639:trends*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics; D034622:RNA Interference
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib