New Test May Show When BRAF Inhibitors Work

Even though about half of melanomas have BRAF mutations, some of these still fail to respond to BRAF inhibitors. Now, there may be a way to tell whether BRAF inhibitors are working, according to findings presented at the 2013 International Conference on Molecular Targets and Cancer Therapeutics. The researchers found that a BRAF inhibitor kept tumors from growing in six out of nine people with BRAF-mutant melanomas, and that those who benefitted from the treatment also had less activation of a protein called S6 at two weeks. If this link is verified in large clinical trials, S6 activation levels could predict BRAF inhibitor effectiveness during the early stages of treatment.

New Drug May Overcome Cancer Treatment Resistance

An experimental drug could keep melanomas and breast cancer from resisting targeted therapies, according to findings reported at the 2013 International Conference on Molecular Targets and Cancer Therapeutics. Called LEE011, the new drug inhibits proteins called cyclin-dependent kinases (CDKs), which make cells divide. The targeted CDKs are abnormally active in many cancers, including melanomas with BRAF mutations and breast cancers with PIK3CA mutations. The researchers found that LEE011 keeps cultured tumor cells from dividing and that combining the drug with targeted treatments prevents resistance in melanomas and breast cancer in mice. Now, these combination treatments are being tested in several phase I clinical trials on a variety of cancers in adults, as well as in children.

New Drug Overcomes Resistance to BRAF Inhibitors in Mice and Cultured Human Cells

An experimental drug may strengthen treatments that target melanomas with mutations in the BRAF gene, reported researchers from the pharmaceutical company Merck at the American Association for Cancer Research’s 2013 meeting. Treatments that target BRAF often stop working because tumors activate a related protein called ERK, which is the target of Merck’s new drug. Called SCH772984, the drug inhibits ERK in cultured human tumor cells with BRAF, NRAS, or KRAS mutations; slows cell division in human tumor cells that resist treatments that target BRAF or MEK; and shrinks tumors in mice. The researchers have begun a phase I clinical trial of an ERK inhibitor in people with tumors.