Targeting the Enzyme of Cancer

Medical News Today published an article written by Catharine Paddock PhD and fact checked by Carolyn Robertson on targeting the enzyme to halt ovarian cancer. The most common form of ovarian cancer is high-grade serous. The cancer develops resistance to chemotherapy and returns in most people. The new study raises hopes for using a different kind of treatment.

Researchers found in working with cell cultures that an enzyme they call isocitrate dehydrogenase 1 (IDH1) encourages the proliferation of high-grade serous ovarian cancer cells. When the cell was blocked by the enzyme chemically or by silencing its gene, the cancer cells lost their ability to divide and multiply. This loss of enzyme activity seemed to put the cancer cells into a state of senescence. When the cells enter this dormant state, they cannot complete their cell cycle. The detailed account of the study was published in the journal Molecular Cancer Research.

Senior study author Katherine M. Aird, Ph.D., assistant professor of cellular and molecular physiology at Penn State College of Medicine in Hershey, PA believes this is one of the biggest problems of cancer cells as they can grow forever without stimulus. The cells can no longer divide and grow by inducing senescence.

About 1 in 78 woman will develop ovarian cancer during their lifetime. The survival chance of more than 5 years after diagnosis is more than 90% when it occurs in the very early stages. However, there are no tests for early detection so this occurs only in around 20% of the cases and most are not found until cancer has started to spread.

The new study concerns high-grade serous ovarian cancer, which is the most common type. About 70% of those with high-grade serous ovarian cancer will have a relapse as the cancer has a tendency to develop resistance to chemotherapy. An urgent need for new approaches to treat this disease is needed.

Aird and her colleagues compared how healthy and cancerous fallopian tube cells used sugar by measuring the byproducts of cell metabolism using mass spectrometry. The results were that the cancer cells favored using sugar in the citric acid cycle. Healthy cells favored converting sugar to lactate using aerobic glycolysis. They believe that targeting glycolysis may not be the best approach as healthy cells use this route for converting sugar to energy this can also damage healthy tissue. IDH1 plays a role in the citric acid cycle and the enzyme stopped cell division. Blocking the enzyme can also arrest the cell cycle of cancer cells that have spread to other parts of the body. FDA has already approved a drug that targets the mutant form of IDH1.

The goal is to try and repurpose this approved drug as a treatment for this form of ovarian cancer.

Dr Fredda Branyon