Hooman Sazegar

TL;DR: It is shown that melanomas escape B-RAF(V600E) targeting not through secondary B-RF(V 600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies.

TL;DR: Testing the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines showed a range of sensitivities to PLX 4032 and metabolic imaging using PET probes can be used to assess sensitivity.

TL;DR: There was a highly significant increase in ITI by CD8+ cells in biopsy samples taken after tremelimumab treatment, despite which only a minority of patients have objective tumor responses.

TL;DR: The preserved viability and function of lymphocytes exposed to high concentrations of PLX4032 suggest that this agent could be a potential candidate for combining with immunotherapy strategies for the treatment of patients with BRAFV600E mutant melanoma.

TL;DR: The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines, however, determinants of veurafenIB and met formin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination is understood.