A new paper has just been published on the mechanisms associated with BRAF resistance by Corcoran et al., (2011).  One of the things I liked about this paper, other than it’s clarity and simplicity, is that you can find it in OncoTarget, an open access cancer journal (see references below), with a prestigious editorial board including Carlo Croce, Bert Vogelstein, Pier Palo Pandolfi, Wafik El Deiry, and Brian Druker to mention a few of the researchers.

The article essentially describes ERK and non-ERK dependent methods by which resistance occurs to BRAF inhibitors such as PLX4032 (vemurafenib).  These are summarised in the table below:

Mechanisms of resistance associated with BRAF

As a result of these findings on the underlying biology to date, the authors suggest that different treatment strategies can be considered:

Potential treatment strategies for overcoming BRAF resistance

As our knowledge of the science of metastatic melanoma improves, so do our opportunities for therapeutic intervention and improvement in outcomes.

Metastatic melanoma is likely to be a hot topic at the forthcoming ASCO annual meeting next month with updated data from the vemurafenib and ipilimumab clinical trials.  I will add a more detailed post once the new data has been presented.

In the meantime, this paper is well worth reading – check it out!


ResearchBlogging.orgCorcoran RB, Settleman J, & Engelman JA (2011). Potential Therapeutic Strategies to Overcome Acquired Resistance to BRAF or MEK Inhibitors in BRAF Mutant Cancers. Oncotarget PMID: 21505228