Fine tuning chemotherapy to match BRCA1 status

• Published in: Biochemical pharmacology Vol. 80; no. 5; pp. 647 - 653
• Main Authors: Price, Melissa, Monteiro, Alvaro N.A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.09.2010
• Subjects: Antineoplastic Agents - therapeutic use; Biomarkers, Tumor; BRCA1; Cancer; Chemotherapy; Cloning, Molecular; DNA Damage; Genes, BRCA1; Humans; Neoplasms - drug therapy; Neoplasms - genetics; Prognosis; Synthetic lethality; Tumor suppressor; SSB; NSCLC; DNA damage; HR; PARP; siRNA; BRCA1; Synthetic lethality; Tumor suppressor; DSB; Chemotherapy; DDR; NER; NHEJ; Cancer
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2010.05.015

Targeted cancer therapies have been primarily directed at inhibiting oncogenes that are overexpressed or constitutively active in tumors. It is thought that as the cell's circuitry gets re-wired by the constitutive activation of some pathways it becomes exquisitely dependent on this activity. Tumor cell death normally results from inhibiting constitutively active pathways. The dependence of tumor cells on the activity of these pathways has been called oncogene addiction. Approaches that aim to exploit loss of function, rather than gain of function changes have also become a powerful addition to our arsenal of cancer therapies. In particular, when tumors acquire mutations that disrupt pathways in the DNA damage response they rely on alternative pathways that can be targeted pharmacologically. Here we review the use of BRCA1 as a marker of response to therapy with a particular focus on the use of Cisplatin and PARP inhibitors. We also explore the use of BRCA1 as a marker of response to microtubule inhibitors and how all these approaches will bring us closer to the goal of personalized medicine in cancer treatment.