Melanoma is the most serious type of
skin cancer and one of the most common
cancers in the world. Advanced
melanoma is often resistant to conventional
therapies and has high potential for
metastasis and low survival rates.
Vemurafenib is a small molecule inhibitor of the BRAF
serine-threonine kinase recently approved by the United States Food and Drug Administration to treat patients with metastatic and unresectable
melanomas that carry an activating BRAF (V600E) mutation. Many clinical trials evaluating other
therapeutic uses of
vemurafenib are still ongoing. The
ATP-binding cassette (
ABC) transporters are
membrane proteins with important physiological and pharmacological roles. Collectively, they transport and regulate levels of physiological substrates such as
lipids,
porphyrins and
sterols. Some of them also remove
xenobiotics and limit the oral bioavailability and distribution of many chemotherapeutics. The overexpression of three major ABC
drug transporters is the most common mechanism for acquired resistance to anticancer drugs. In this review, we highlight some of the recent findings related to the effect of ABC
drug transporters such as ABCB1 and ABCG2 on the oral bioavailability of
vemurafenib, problems associated with treating
melanoma brain metastases and the development of acquired resistance to
vemurafenib in
cancers harboring the BRAF (V600E) mutation.