The findings are published in the December 5, 2013 online issue of Science.

“This discovery has considerable clinical implications because if cancer cells can evade therapy by a ‘hide-and-seek’ mechanism, then the current focus (of drug therapies) is unlikely to translate into better outcomes for patients,” said Mischel.

In recent years, new cancer therapies have emerged that target tell-tale gene mutations to identify specific cancer cells for destruction. Unfortunately, a variety of “resistance mechanisms” have also emerged, among them incomplete target suppression, second-site mutations and activation of alternative kinases or enzymes that maintain growth-promoting signals to the cancer itself.

“Most research is aimed at developing better drugs or better drug combinations to suppress these downstream signals,” Mischel said. “However, one thing that has not been carefully considered is whether cancer cells can modulate the levels of – and thus their dependence on – the target of the drug, evade therapy, and then re-acquire the oncogene to promote tumor growth when the drug is withdrawn.”

Mischel and colleagues, including Webster K. Cavenee, PhD, and Frank B. Furnari, PhD, of the Ludwig Institute and the UC San Diego School of Medicine, investigated the behavior of glioblastoma multiforme (GBM), the most common malignant primary brain cancer in adults. More than 9,000 new cases of the disease are diagnosed each year in the United States and effective treatments are limited. The tumors are aggressive and resistant to current therapies, such as surgery, radiation and chemotherapy. The median survival rate for newly diagnosed GBM patients is just 14 months.