New class of Merck drugs targets therapy-resistant cancer

Researchers at Merck ($MRK) are developing a class of new drugs that could help improve treatment options for patients with certain cancers driven by genetic mutations.

When mutations happen in critical genes such as BRAF or KRAS/NRAS, they alter the normal processes of cell proliferation, differentiation and death and can cause patients to become resistant to therapies that target BRAF directly. The research was presented at the annual meeting of the American Association for Cancer Research this week in Washington, D.C.

"Patients with cancer treated with BRAF and/or MEK inhibitors are susceptible to the development of resistance primarily via reactivation of ERK," Ahmed Samatar, team leader of discovery oncology at Merck Research Laboratories, said in a statement. "ERK inhibitors may provide a means to treat patients with these drug-resistant tumors, and an ERK inhibitor in combination with a BRAF or MEK inhibitor may also provide a strategy to overcome drug resistance."

Merck is working on a new class of investigational medications that targets ERK proteins, which are components of the MAPK signaling pathway. In this pathway, they function downstream of RAS, BRAF and MEK. Drugs that inhibit BRAF and MEK previously have been tested in clinical trials in which they were effective in patients with melanoma who also have the BRAF gene mutations.

The researchers used a novel ERK inhibitor called SCH772984 to test its ability to inhibit tumor cell growth. They observed that the inhibitor stopped the growth of tumor cells with mutations in BRAF, NRAS or KRAS in cultured human tumor cells and caused tumor regression in mice. The researchers also found that SCH772984 inhibited MAPK signaling and cell proliferation in tumor cells that are resistant to BRAF and MEK inhibitors either alone or in combination.

Samatar's team is beginning a Phase I clinical trial of an investigational ERK inhibitor in patients with solid tumors.

- here's the release