PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas |
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Authors: | 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 |
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Affiliation: | Department of Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA. |
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Abstract: | 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. |
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Keywords: | PLX4032 RG7204 B-Raf melanoma therapy V600E |
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