2018 LCRF Scientific Grant Program
Pawel Mazur, PhD
The University of Texas MD Anderson Cancer Center
Mechanisms of protein synthesis regulation in lung cancer
A major unmet need for lung cancer treatment is the identification of new therapeutic targets, which requires elucidating the critical genes and signaling pathways driving this disease. Dr. Mazur’s research strategy directly addresses these priorities by proposing to identify a new target for which drugs can be rapidly developed. Specifically, this project tests the idea that a class of enzymes named “lysine methyltransferases” (KMTs) plays a key role in promoting cancer. KMTs are enzymes that add methyl groups to lysine residues on other proteins. Methylation of proteins in cancer can modify their activity to promote tumor growth. Importantly, KMTs can be inhibited by small molecules and thus constitute ideal targets for drug development. Surprisingly, however, little to nothing is known about the role of over 100 KMTs in cancer.
Dr. Mazur’s study identifies new KMT that regulates the most energy-consuming process in the cell – protein production. Dysregulation of protein production is a hallmark of cancer and is linked to aberrant cell proliferation, survival, and alterations in both immune responses and cancer energetics. While several key molecules involved in protein synthesis were found to be methylated in cancer, the role of lysine methylation in calibrating protein production remains untested. Knowledge into the regulation of protein production by methylation may also uncover a new paradigm for how crosstalk between major signaling systems is integrated to modulate critical cellular behaviors. Thus, identifying reversible molecular mechanisms such as methylation that stimulate protein production in tumors may uncover opportunities to target specific lung cancer vulnerabilities with minimal off-target toxicity.