Oncogene Overdose: Too Much of a Bad Thing for Oncogene-Addicted Cancer Cells.

ABSTRACT: Acquired resistance to targeted inhibitors remains a major, and inevitable, obstacle in the treatment of oncogene-addicted cancers. Newer-generation inhibitors may help overcome resistance mutations, and inhibitor combinations can target parallel pathways, but durable benefit to patients remains elusive in most clinical scenarios. Now, recent studies suggest a third approach may be available in some cases-exploitation of oncogene overexpression that may arise to promote resistance. Here, we discuss the importance of maintaining oncogenic signaling at "just-right" levels in cells, with too much signaling, or oncogene overdose, being potentially as detrimental as too little. This is highlighted in particular by recent studies of mutant-BRAF in melanoma and the fusion kinase nucleophosmin-ana

SUBMITTER: Amin AD 

PROVIDER: S-EPMC4681422 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature