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PLX4032, a potent inhibitor of the B‐Raf V600E oncogene, selectively inhibits V600E‐positive melanomas
Author(s) -
Lee John T.,
Li Ling,
Brafford Patricia A.,
van den Eijnden Marcia,
Halloran Molly B.,
Sproesser Katrin,
Haass Nikolas K.,
Smalley Keiran S.M.,
Tsai James,
Bollag Gideon,
Herlyn Meenhard
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2010.00763.x
Subject(s) - melanoma , v600e , oncogene , cancer research , medicine , cell cycle , cancer , biology , mutation , gene , genetics
Summary Targeted intervention of the B‐Raf V600E gene product that is prominent in melanoma has been met with modest success. Here, we characterize the pharmacological properties of PLX4032, a next‐generation inhibitor with exquisite specificity against the V600E oncogene and striking anti‐melanoma activity. PLX4032 induces potent cell cycle arrest, inhibits proliferation, and initiates apoptosis exclusively in V600E‐positive cells in a variety of in vitro experimental systems; follow‐up xenograft studies demonstrate extreme selectivity and efficacy against melanoma tumors bearing the V600E oncoproduct. The collective data support further exploration of PLX4032 as a candidate drug for patients with metastatic melanoma; accordingly, validation of PLX4032 as a therapeutic tool for patients with melanoma is now underway in advanced human (Phase III) clinical trials.