FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma.

doi:10.1016/j.ccell.2025.02.001

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FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma.

Cancer cell - 10 Mar 2025

Lubrano Simone, Cervantes-Villagrana Rodolfo Daniel, Faraji Farhoud, Ramirez Sydney, Sato Kuniaki, Adame-Garcia Sendi R, Officer Adam, Arang Nadia, Rigiracciolo Damiano C, Anguiano Quiroz Paola Y, Martini Claudia, Wang YiYu, Ferguson Fleur M, Bacchiocchi Antonietta, Halaban Ruth, Coma Silvia, Holmen Sheri L, Pachter Jonathan A, Aplin Andrew E, Gutkind J Silvio

Abstract excerpt

Widespread BRAF mutations result in persistent RAS-RAF-MEK-ERK (MAPK) signaling in melanoma. BRAF (BRAFi) and MEK (MEKi) inhibitors are approved for BRAF V600E melanomas, including those progressing on immunotherapy; however, rapid resistance to these agents highlights the need for novel strategies. Here, transcriptome analysis of BRAF V600E melanomas from patients resistant to BRAFi and MEKi shows activation of...

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Identifiers

PMID: 40020669
DOI: 10.1016/j.ccell.2025.02.001
PMCID: PMC11903146

Genes

BRAF
RND3

Variants

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