Drug Combo Blocks Rare Cancer’s Escape Route

By blocking a cancer’s escape route, a two-drug combination has shown promise against a rare but aggressive nerve tumor in animal tests, researchers at Columbia University’s Herbert Irving Comprehensive Cancer Center and Memorial Sloan Kettering Cancer Center have found.

Based on the new findings, the researchers say the combination holds great potential and should be considered for clinical testing in patients.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but highly aggressive cancers of the soft tissue that encases nerves. MPNSTs occur in approximately 1 in 100,000 people in the general population, but in about 10 percent of people with neurofibromatosis type I. MPNSTs are highly resistant to chemotherapy, and there are no effective treatments.

Based on the analysis of how MPNST tumors grow, cancer researchers initially thought that rapamycin—an FDA-approved drug that prevents rejection of transplanted organs—might block tumor growth. But the drug did not do well in clinical trials.

Research led by Gary K. Schwartz, MD, professor of medicine and HICCC associate director, later found that MPNSTs can dodge rapamycin’s ability to block tumor proliferation and tap a different “escape” pathway to maintain tumor cell growth.

In the current study, Dr. Schwartz and Parag P. Patwardhan, PhD, associate research scientist in the Department of Medicine, found that an experimental drug, PLX3397, can block this escape route.

PLX3397 was able to inhibit the tyrosine kinases critical to the escape route, and when used in combination with rapamycin, significantly inhibit the growth of MPNSTs in vitro and in human tumors implanted in mice.

PLX3397 is currently in trials for several cancers, including lymphoma, glioblastoma, and metastatic breast cancer.