Lay summary
The precision medicine concept advocates delivering targeted therapies selectively to those who will benefit most. Drugs targeting oncogenic mutations driving cancers have been a major focus of such strategies. One of the first such drugs was vemurafenib and has very pronounced clinical impact in melanomas driven by V600 mutations in the BRAF gene. However, efficacy of vemurafenib is limited as clinical resistance arises rapidly and tumours lacking V600 mutations don't respond or respond adversely. In preclinical models we have discovered that VEGF inhibitors synergise with vemurafenib, blocking melanoma growth regardless of BRAF mutation status. This has potential to greatly increase the number of patients who would benefit from vemurafenib and may also overcome drug resistance. Our studies will seek to understand how this combination therapy achieves such dramatic effects and we will use this information to rationally design clinical trials to test efficacy of this combination in patients.