American Association for Cancer Research

Targeting PP2A and the Glutamine-Sensing Pathway as Cancer Treatment

Summary

Normal body cells grow, divide and die in an orderly fashion. Cancer arises if cells in a particular tissue begin to grow out of control. Most fast-growing cancer cells acquire mutations enabling them to take in more nutrients from the environment in order to divide. However, rapid tumor growth often leads to nutrient deprivation conditions in tumor cells. Cancer cells develop strategies to survive a low-nutrient environment. Understanding these mechanisms is important for developing new drugs that could starve tumor cells to death and block cancer progression. Glutamine and glucose are two major nutrients that support cancer cell growth and survival. This project will determine the molecular basis of tumor cell survival under glutamine deprivation in order to develop novel drugs targeting this pathway. To date, drugs designed to inhibit cancer cells from using nutrients have been successful in killing cancer cells. However, all these drugs have to be used at a high dose, resulting in toxic side effects. Thus, sensitizing cancer cells to these drugs by blocking cell survival mechanisms is necessary to inhibit tumor growth. Kong will test the idea that we can starve cancers to death by blocking the nutrient supply and PP2A, which is a phosphatase that plays a critical role in mediating cell survival upon glutamine deprivation. If successful, this strategy is likely to be applicable to numerous tumor types, and therefore, this research will potentially benefit a large population of cancer patients.

Investigator

Mei Kong, Ph.D., is assistant professor in the division of tumor cell biology at Beckman Research Institute of City of Hope in Duarte, Calif.

Updated: April 4, 2011