Oncogene addiction pathways

The development of drugs targeting tumours driven by so-called 'oncogene addictions' has lead to some success. Examples include imatinib targeting the bcr-abl translocation in CML and mutated c-kit in GIST, trastuzumab and laptinib in HER-2 positive breast cancers BRAF inhibitors in melanomas with BRAF mutations. Molecular studies in prostate cancer have to date identified mutations of this type in less than 20% of all sporadically occurring prostate cancers. Analysis of a cohort of 206 prostate cancer cases found the common BRAF mutation V600E in 10.2% (or 21/206 cases) [51], whilst PI3 kinase mutations were found in only 3% of a separate cohort [52]. Drugs inhibiting BRAF as well as PI3 kinase mutations may lead to meaningful responses in patients with tumors been driven by these mutations. It is hoped that further "oncogene addiction" pathways will be uncovered and be able to be drugged.

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