Kinase inhibitors have been used successfully in the clinic, but relapse is common due to the emergence of resistance. Inhibition of HSP90 leads to the depletion of oncogenic ‘client’ proteins and
the simultaneous inhibition of many signalling pathways. As such, the use of HSP90 inhibitors to overcome resistance has been widely investigated.
Onalespib (AT13387) is a potent, second generation HSP90 inhibitor, which has been studied in many preclinical models of kinase inhibitor resistance. Recent findings indicate that an upfront
combination of onalespib and either vemurafenib or crizotinib, in models of mutant BRAF melanoma or ALK-translocated non-small cell lung cancer (NSCLC), can delay the emergence of resistance
to these therapies (Smyth et al 2014, Wallis et al 2014). Here we have extended this work to a combination of onalespib and erlotinib in an EGFR-driven NSCLC model.
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2015 AACR: Onalespib delays the emergence of resistance to erlotinig in EGFR-driven xenograft model