BRAF and melanoma: Interestingly, their analysis demonstrated the existence of only two major alternative metastable states in the specific melanoma population that they studied, whereas studies of melanoma in vivo suggest that there are up to four transcriptional programmes that can facilitate resistance to BRAF or MEK inhibitor combination therapy.21 Therefore, each cancer cell population might only have a limited number of possible metastable gene expression programmes that it can exploit to avoid therapy.