First-in-class ERK1/2 Inhibitor Safe, Shows Early Efficacy In Patients With Advanced Solid Tumors

Source: Medical Xpress, December 2017

The novel ERK1/2 kinase inhibitor ulixertinib displayed an acceptable safety profile and had clinical activity in patients whose tumors had mutations in the MAPK cell-signaling pathway, according to data from a phase I clinical trial published in Cancer Discovery, a journal of the American Association for Cancer Research.
“A great number of cancers, including melanoma and lung cancers, have mutations in the MAPK/ERK pathway, and while current therapies target proteins in this cascade, many  develop resistance to current drugs,” said Ryan J. Sullivan, MD, assistant professor of hematology and oncology and member of the Termeer Center for Targeted Therapies at Massachusetts General Hospital. “The common denominator in these failed therapies is that the cancer has found a way to activate ERK. Therefore, the development of ERK inhibitors is a crucial next step to target this aberrant pathway.”
The MAPK/ERK pathway is essential for key cellular processes, and mutations along this pathway may result in uncontrolled cellular growth, which can lead to cancer. The RAS gene, an upstream regulator within the MAPK/ERK cascade, is mutated in roughly 30 percent of human cancers. Mutations in BRAF, another gene in this pathway, often occur at codon V600 in malignant melanoma, where combined BRAF/MEK inhibition is the current standard of care. Atypical BRAF mutations (non-V600) are found in a variety of cancers. There is no targeted therapy for patients with atypical BRAF-mutant cancers, said Sullivan.
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