Resistance of BRAFV600E-mutant melanoma to Vemurafenib: a senescence-induced swing from differentiation to blastulation followed by proliferation - PubMed
6 hours ago
- #Melanoma
- #Cellular Reprogramming
- #Drug Resistance
- Resistance to Vemurafenib (VEM) in BRAFV600E-mutant melanoma involves a transition through senescence, blastulation, and proliferation phases.
- Initial treatment suppresses pERK, leading to senescence, autophagy/mitophagy, and neuro-melanogenesis.
- MAPK-ERK signaling later resumes, overcoming cell cycle checkpoints and downregulating senescence and melanogenesis.
- Cells exhibit hyperploidy, multinucleation, and structures resembling oocytes or blastulae, some entering diapause.
- Transcriptomic analysis shows a shift from neuro-melanogenesis to female meiosis-like and mitosis states.
- Resistance involves three cell fate transitions: senescence/differentiation, reprogramming/blastulation, and proliferative recovery.
- Findings are supported by coexpression of senescence and gametogenetic genes in late-stage melanoma patient samples.