Posted November 26, 2014
Jing Chen, Ph.D., from the Emory University, is a recipient of a Fiscal Year 2011 Lung Cancer Research Program Investigator-Initiated Translational Research Award.
1. What is the most important thing that stakeholders should know about your research?
We showed that metabolic enzyme PGAM1 is a crucial linkage between glycolysis/glucose catabolism, anabolic biosynthesis, cancer cell proliferation and tumor growth. Thus, our studies provided novel insights into the molecular mechanisms underlying the Warburg effect in cancer metabolism and tumor development. Moreover, the idea of targeting cancer cell metabolism as a therapeutic strategy is novel and timely. Our results were the "proof of principle" suggesting that PGAM1 is a novel therapeutic target in clinical treatment of lung cancer and provided the rationale for developing novel PGAM1 small molecule inhibitors as new anti-cancer agents in the treatment of lung cancer patients.
2. How did you arrive at this information or approach?
How cancer cells coordinate the production of energy and "building blocks" for themselves, and how crucial this is for tumor development and growth are largely unknown. We approached these questions by performing phosphoproteomics-based studies to identify critical metabolic enzymes that coordinate bioenergetics and biosynthesis in human cancers using lung cancer as a representative platform. We identified PGAM1 and developed the project.
3. What is the next step to bringing your research closer to helping lung cancer patients?
Lung cancer is the leading cause of cancer-related death in the United States and worldwide. Although there have been major breakthroughs that resulted from increased understanding of how lung cancers initiate, progress, and metastasize, the development of targeted agents in lung cancer is still in its infancy. This is in part due to the lack of potential molecular targets for inhibiting lung cancer initiation and metastasis, outside of the recently approved EGFR-targeted therapies. To improve the clinical treatment and outcome of lung cancer patients, it is critical that the research community identify new promising therapeutic targets and develop strategies to block such targets.
Our demonstration of PGAM1 as a promising therapeutic target and development of PGAM1 small molecule inhibitors may help lung cancer patients. When our studies are completed, we expect to have second-generation PGAM1 drugs that may be applied to initiate clinical trials to treat lung cancer patients.
Hitosugi T, Zhou L, Fan J, Elf S, Zhang L, Xie J, Wang Y, Gu TL, Alečković M, LeRoy G, Kang Y, Kang HB, Seo JH, Shan C, Jin P, Gong W, Lonial S, Arellano ML, Khoury HJ, Chen GZ, Shin DM, Khuri FR, Boggon TJ, Kang S, He C, Chen J. 2013. Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation. Nature Communications; 4:1790 .
Chen J, Hitogushi T, and Kang S. 2014. Pgam1 inhibitors and methods. Emory University, Atlanta, Georgia. PCT/US2012/059740.