Treatment with RAF inhibitors confers a survival benefit to patients with mutant-BRAF-driven melanoma. Paradoxically, in tumours that also contain oncogenic mutations in RAS or its upstream signalling receptors, RAF inhibitors can stimulate tumour growth by further activating MAPK signalling. Now, new research shows that the next-generation RAF inhibitors PLX7904 and PLX8394 can inhibit downstream MAPK signalling in cultured cells with BRAF mutations. Importantly, these compounds did not activate MAPK signalling in those cell lines with additional mutations that cause basal activation of this pathway.
References
Zhang, C. et al. RAF inhibitors that evade paradoxical MAPK pathway activation. Nature 526, 583–586 (2015)
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Romero, D. Paradox breakers — promising novel RAF inhibitors. Nat Rev Clin Oncol 13, 2 (2016). https://doi.org/10.1038/nrclinonc.2015.195
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DOI: https://doi.org/10.1038/nrclinonc.2015.195
