Scientists are on a long journey for answers about tumors and how to stop their growth in humans. Despite piles of research, the disease continues to be difficult to treat because of its ability to adapt and thrive even when exposed to unfavorable conditions.

About four years ago, it was learned that low oxygen levels in cells can cause uncontrollable tumor growth in some cancers. This tumor adaptation — called hypoxia, or a lack of oxygen — is one example of a phenomenon that should weaken the tumor, but instead drives more aggressive disease behavior. A new study from scientists at The Wistar Institute in Philadelphia has identified a critical pathway that could be responsible for this unexpected response.

"Hypoxia is a nearly universal hallmark of aggressive tumor growth, and up until now, we really haven't been able to home in on a pathway responsible for this behavior," said Dario C. Altieri, M.D., Wistar's President, CEO and lead author of the study. He is also director of The Wistar Institute Cancer Center and the Robert & Penny Fox Distinguished Professor.

"Our study pinpoints a novel way in which tumor cells not only survive but actually continue to divide in spite of a low oxygen environment,” he added. “In essence, this provides a much-needed answer for exactly how tumor cells are able to get the energy they need to persist when faced with unfavorable conditions."

The scientists have reported that one critical pathway could be a valuable therapeutic target in cancer. Altieri and his team also showed how the activation of this pathway leads to a poor prognosis for patients with a certain type of brain tumor.

"(Certain) drugs have produced limited clinical responses to date, but we believe with further investigation that we may be able to repurpose these drugs as a viable approach to impair a tumor's ability to adapt to hypoxia," said Young Chan Chae, Ph.D., an associate staff scientist in the Altieri lab and first author of the study.

Source: Altieri D, Chae Y, Caino M, et al. Low oxygen, high risk: How tumors adapt to become more aggressive, Cancer Cell , 2016.