Oncogene Biology

In the search for therapeutic combinations for the treatment of cancer, the pairing of targeted inhibitors of oncogenic driver pathways with immunotherapy has largely been overlooked. In Nature,describe how the novel KRAS-G12C inhibitor AMG 510 can potentiate immune rejection in combination with immune checkpoint blockade.

Research ArticleCancer Miriam Molina-Arcas1,2, Christopher Moore1, Sareena Rana1,2, Febe van Maldegem1, Edurne Mugarza1, Pablo Romero-Clavijo1, Eleanor Herbert3,4, Stuart Horswell5, Lian-Sheng Li6, Matthew R. Janes6, David C. Hancock1 and Julian Downward1,2,* 1Oncogene Biology, Francis Crick Institute, London NW1 1AT, UK. 2Lung Cancer Group, Institute of Cancer Research, London SW3 6JB, UK. 3Experimental Histopathology, Francis Crick Institute, London NW1 1AT, UK.

Highlights • RAC1P29S activates PAK, AKT, and the SRF/MRTF transcription program in melanocytes • RAC1P29S induces a melanocytic to mesenchymal transition through SRF/MRTF and PAK • RAC1P29S cooperates with BRAF mutation or NF1 deletion to promote melanomagenesis • RAC1P29S induces resistance to BRAF inhibitors through SRF/MRTF Summary RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61.