About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biolog-ical traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less de-pendent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma.

Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma

Nepote A.;Avallone G.;Ribero S.;Cavallo F.;Roccuzzo G.;Mastorino L.;Paruzzo L.;Poletto S.;Quaglino P.;Aglietta M.
2022-01-01

Abstract

About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biolog-ical traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less de-pendent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma.
2022
11
3
828
835
BRAF mutation; BRAF V600K; Cutaneous melanoma; Immunotherapy; Target therapy
Nepote A.; Avallone G.; Ribero S.; Cavallo F.; Roccuzzo G.; Mastorino L.; Conforti C.; Paruzzo L.; Poletto S.; Schianca F.C.; Quaglino P.; Aglietta M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1863388
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