Targeting Glycolysis in Prostate Cancer Using Antisense Oligonucleotides against Monocarboxylate Transporter 4
Joy Wang, Kendra Fu
York House School
Floor Location : M 235 H

Cancer is an uncontrollable growth of cells caused by mutated genes. Cancer cells rely mainly on the glycolysis part of the energy production process, resulting in increased glucose consumption and production of lactate to make an acidic tumor microenvironment. An acidic microenvironment is essential for cancer cell proliferation and invasion. Prostate cancer, in particular, is one of the most commonly diagnosed cancers in men, and there is currently no effective therapy to treat it. The objective of our project is to target the protein Monocarboxylate Transporter 4, or MCT4, which pumps the acidic product out of the cell in order to neutralize the acidic tumor microenvironment, and eventually, lead to tumor inhibition. In this project, we will use different samples of antisense oligonucleotides in order to treat prostate cancer cells. Antisense oligonucleotides, or ASOs, are chemically modified DNA or RNA strands that complement a particular faulty genetic sequence. They are designed to block protein translation so that the sequence ceases to be expressed. The cell proliferation and dose dependency of the different ASO samples will be tested. We hope to 1) identify an ASO that decreases MCT4 levels and 2) cause a decrease in glucose consumption and lactate generation, restore normal pH, and ultimately inhibit cancer growth.