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Harnessing Genetic Dependencies In Cancer Therapy
Author(s) -
Ashworth Alan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.356.2
Subject(s) - synthetic lethality , homologous recombination , rna interference , computational biology , cancer , dna repair , biology , parp inhibitor , gene , mutation , genetics , bioinformatics , poly adp ribose polymerase , rna , polymerase
Many tumours harbour defects in their ability to maintain genomic integrity. This contributes to the mutational burden and likely fosters pathogenesis. We have been exploring therapeutic strategies to exploit these defects. We have used a synthetic lethal approach to target the defect in DNA repair by homologous recombination in tumours with a BRCA1 or BRCA2 mutation. This strategy using PARP inhibitors is showing considerable promise in the clinic. Here, I will describe the approach as well recent work defining determinants of sensitivity and resistance to PARP inhibitors. The application of the synthetic lethal approach to other cancer types will also be discussed. In addition, we have been using high‐ and medium‐ throughput RNAi screens to uncover new therapeutic targets for cancer as well as biomarkers of patients who might respond to specific treatments. In particular I will discuss the integration of genomic, gene expression and RNAi data to generate functional maps of cancers.