Manuscript published in Cancers in July 2024.
The treatment of BRAF-mutant melanoma with BRAF inhibitors is severely limited in clinical practice, in part due to the emergence of drug tolerance via non-genetic adaptation to therapies. Improving our understanding of the molecular mechanisms that underlie drug tolerance may lead to improved treatment strategies. Here, we describe a novel calcium-dependent signaling mechanism induced by BRAF inhibitor (BRAFi) treatment that provides compensatory mitogenic signaling to drug-tolerant persister cells in the form of MAPK reactivation. This calcium signaling mechanism has not previously been recognized in BRAFi-tolerant melanoma, may initiate a novel line of scientific inquiry, and presents a host of novel targets for therapeutic development in this field.
Stauffer PE, Brinkley J, Jacobson DA, Quaranta V, Tyson DR. Purinergic Ca2+ Signaling as a Novel Mechanism of Drug Tolerance in BRAF-Mutant Melanoma. Cancers (Basel). 2024; 16(13) 2426. doi:10.3390/cancers16132426. PubMed PMID: 39001489. PMCID: PMC11240618.
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