Source: www.mc.vanderbilt.edu
Author: Dagny Stuart

A new drug which targets a genetic mutation found in more than 50 percent of melanoma cases, 10 percent to 15 percent of colorectal tumors and 8 percent of other solid tumors, caused tumor shrinkage and extended progression-free survival among patients during a recent Phase 1 clinical trial.

Igor Puzanov, M.D., assistant professor of Medicine, and Jeffrey Sosman, M.D., Ingram Professor of Cancer Research, led Vanderbilt-Ingram Cancer Center’s participation in the multi-center study. Puzanov delivered the initial findings during a poster session at the recent American Society of Clinical Oncology (ASCO) conference in Orlando, Fla.

Puzanov and Sosman were among nearly a dozen VICC cancer investigators who were invited to give oral or poster presentations on their latest research findings during the ASCO conference.

PLX4032 is a novel, highly selective drug that targets the BRAFV600E cancer-causing genetic mutation. In addition to tumor shrinkage and delay in tumor progression, some patients reported clinical improvement in symptoms.

“The BRAFV600E mutation activates the MAP kinase signaling pathway, causing cells to proliferate. One of the hallmarks of cancer is this uncontrolled, unregulated cell proliferation,” said Puzanov. “The new drug is a very selective inhibitor which appears to target only this mutation, and it blocks the unregulated cell growth and causes cell death.”

In patients without the mutation, no clinical response to treatment was observed and progression-free survival was less than two months, consistent with historical data.

“This is personalized medicine at its best,” said Sosman. “If continued trials confirm the agent works only in patients with this mutation, we can target those patients for this drug and spare others from undergoing a treatment that won’t work.”

Christine Chung, M.D., assistant professor of Medicine, presented on the use of a mass spectrometry-based algorithm to predict which head and neck cancer patients may benefit from treatment with certain drugs.

Chung’s group found that the same predictive algorithm generated from patients with non small-cell lung cancer treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is also predictive of survival outcome in head and neck squamous cell cancer patients treated with the same types of drugs.