Newswise — New Brunswick, N.J. – October 18, 2017 – Tumors acquire nutrition necessary for generating energy and building blocks for growth and survival from the body of the patient in which they reside. Although these nutrients are predominantly provided by the circulating blood supply, our understanding of what these nutrients are and how they are used by tumors is incomplete. Identifying tumor nutrients and how they are used may reveal novel approaches to cancer therapy. Research from investigators at Rutgers Cancer Institute of New Jersey and Princeton University surprisingly finds that circulating lactate rather than glucose is the prominent metabolic fuel source for tumors and most normal tissues. Circulating lactate is used to produce energy, freeing up glucose to support other metabolic functions important for tumor growth.
Rutgers Cancer Institute of New Jersey members, Deputy Director, Chief Scientific Officer, and Associate Director for Basic Science Eileen P. White, PhD, distinguished professor of molecular biology and biochemistry in the School of Arts and Sciences at Rutgers University; and Yanxiang (Jessie) Guo, PhD, Rutgers Cancer Institute researcher and assistant professor of medicine, Rutgers Robert Wood Johnson Medical School and the Ernest Mario School of Pharmacy, along with Joshua D. Rabinowitz, MD, PhD, professor in the Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics at Princeton University, published these findings in the October 18 edition of Nature (doi:10.1038/nature24057). They share more about the research, which they say forms the basis for defining and targeting tumor metabolism for cancer therapy:
Q: Why is this topic important to explore?
A: Much of what we know about nutrient usage in cancer derives from examination of cancer cells growing in laboratory culture with artificial media, which may not represent the authentic nutrition that tumors rely on normally provided by the circulating blood supply. Although technically challenging, we chose to determine the nutrient usage by tumors rather than tumor cells in artificial media. We were surprised to find that lactate, normally considered a waste product of metabolism, was a major nutrient source for several types of aggressive tumors. We also learned that this circulating lactate was used by tumors to produce the energy important for growth.
Q: How did your team approach the work and what did you learn?
A: Using genetically engineered lung and pancreatic cancer tumors in mouse models and mass spectrometry, we and our collaborators examined nutrient usage by tumors and also normal tissues. We found that circulating lactate, rather than glucose, is the major source of TCA cycle carbon and thus energy, an unexpected finding based on previous examination of nutrients used by cultured cancer cells.
Q: What is the implication of this finding?
A: Knowing the nutrients that fuel tumor growth is a first step to targeting cancer metabolism. Cancer is a metabolic disease and there is great potential to exploit this for cancer therapy. It is clear that studying the metabolism of tumors rather than isolated tumor cells in artificial media can uncover novel, physiologically relevant metabolic vulnerabilities potentially targetable for cancer therapy.
This work was supported by grants from the National Institutes of Health: 1DP1DK113643, R01 CA163591, R01 CA130893, K22 CA190521, R01 CA186043, R35 CA197699, R50 CA211437, Cancer Center Support Grant P30 CA072720 (Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey), and 5P30 DK019525. In addition, it was supported by Stand Up To Cancer-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team Research Grant (SU2C-AACR-DT-20-16).