Turning off Cancer Master Switch May Worsen Tumor Growth

Study finds that mitochondria of tumor cells are critical to survival and proliferation.

Recent studies have shown that inhibition of phosphatidylinositol-3 kinase (PI3K), the "master switch" of cancer, can actually worsen tumor growth.

Recently, researchers have found that defective forms of PI3K are present in almost all types of human cancer, making it a logical target for inhibition therapy. It has been shown to play a key role in the growth, durability, and metastasis of tumor cells. In clinical trials, however, results have been modest.

In treatments using only a PI3K inhibitor, tumor growth even worsens.

Researchers at the Wistar Institute, headed by Dario C. Altieri, MD, started to focus on another key element in tumor growth: the mitochondria, and how it reacted when exposed to PI3K inhibitors.

"Our prior studies have confirmed that tumor cells rely on energy produced by mitochondria more significantly than previously thought," Dr. Altieri said. "What we have shown in this study is that, in somewhat of a paradox, treatment with a PI3K inhibitor causes a tumor cell's mitochondria to produce energy in a localized manner, promoting a far more aggressive and invasive phenotype. The treatment appears to be doing the opposite of its intended effect."

The mitochondria, when exposed to a PI3K inhibitor, migrated to the outer cell membrane of the tumor cell. This position proved to be more ideal to provide a concentrated source of energy to other tumor cells, enabling them to grow faster, and move quicker.

Although this somewhat crushes the hopes of turning off the "master switch" of cancer, the study provides more insight into the role of the mitochondria in tumor growth.

"These findings continue to support the idea that the mitochondria of tumor cells are crucial to tumor survival and proliferation," Altieri said. "It's certainly counterintuitive that a drug designed to fight cancer may in actuality help it spread, but by identifying why this is happening, we can develop better strategies that allow these drugs to treat tumors the way they should."

The findings were published online by the journal Proceedings of the National Academy of Sciences.