Metabolic Differences in Tumor Cells May Be New Drug Targets

Understanding distinct metabolic needs of tumor cell subtypes may spur development of drugs that target the special requirements of each cell population.

Grantees: Malathy Shanmugam, PhD, MS, and Adam I. Marcus, PhD
Institution: Emory University School of Medicine 
Area of Focus: Cell Biology and Preclinical Cancer Research
Grant Term: The research described here was not supported by an ACS grant. As previous ACS grantees, Dr. Shanmugam studied targeting altered metabolism in melanoma, and Dr. Marcus studied lung cancer metastasis.

Much research has focused on the main types of cells that make up a tumor. But tumors are actually made up of different subtypes of cells that often behave differently from each other. Less is known about the function of these cell subtypes, especially those involved in metastasis.

During metastasis, cancer cells break away from a tumor and travel to another part of the body where they invade tissue to form a new tumor. There are fewer treatments that are effective for cancers that have spread, and treatment for metastatic cancer tends to be more complicated.

Studies have shown that, most of the time, single cancer cells do not metastasize on their own. Instead, increasing evidence suggests that a collection of cell subtypes collaborate as an “invasion pack” during metastasis. Understanding how these cell subtypes work together to spread cancer is key to developing treatments that can help stop cancer from spreading.

The Shanmugam and Marcus labs at Emory University in Atlanta used the first chemical biology screen to explore how cell subtypes cooperate within invasion clusters of metastatic lung cancer cells. They looked at two tumor cell subtypes that invade new tissue, leader cells and follower cells. They discovered that these two cell populations have certain metabolic requirements—getting energy they need to survive.

This diversity in the metabolic needs of cells is known as metabolic plasticity. Shanmugam and Marcus speculate that in the invasion pack, this diversity may help cancer cells “better adapt to the selective pressures of the tumor microenvironment and maintain the ability to ‘go’ and ‘grow’ as a cooperative unit.” The researchers also showed that they could use these metabolic needs to suppress or block cell growth and tumor invasion.

Why Does It Matter? This research from Shanmugam and Marcus demonstrates that understanding the distinct metabolic needs of tumor cell subtypes can help lead to the development of drugs that target the special requirements of each cell population. This has the potential to limit their ability to work together to spread and grow.

Read more about this study.