Researchers identified a specific protein, IDH1, within the High-grade serous ovarian cancer cells that promote the proliferation of these cancer cells. Targeting this protein with drugs can help halt the spread of ovarian cancer.
High-grade serous ovarian cancer (HGSC) is the deadliest and the most common type of ovarian cancer. In the later stages, this cancer spread outside the ovaries and expand through the peritoneal cavity. There, the tumor attains different structure and function than the primary tumor adherent to the ovaries.
Research exploring various treatment options to stop the progression of high-grade serous ovarian cancer can increase the survival time of numerous cancer patients.
In about 70% of the cases, the HGSC relapses, regardless of the treatment as it develops resistant against chemotherapy. Thus, this new development in understanding the growth of ovarian cancer cells is an exceptional breakthrough in treating this type of cancer.
Researchers from the Penn State College of Medicine, Hershey, Pennsylvania; University of Colorado Anschutz Medical Campus, Denver, Colorado; and AJ Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania have recently published a research that lifted hopes for treating HGSC in a way that ensures increased survival of the patients without tumor progression.
The lead author of this study, Dr. Katherine M. (assistant professor of cellular and molecular physiology at Penn State College of Medicine in Hershey, PA) shared the essential characteristics of the cancer cells growth saying,
"A hallmark of cancer cells is that their metabolic processes are often different from normal, healthy cells." and that the "Cancer cells can grow forever without stimulus."
However, if by any means, there is a halt in the metabolic process of the cancer cells, they will stop metastasizing. Dr. Katherine added, "By inducing senescence, the cells can no longer divide and grow,"
Molecular Cancer Research published this research in August 2019.
Metabolic Comparison of the Healthy and Tumor Cells
In this study, the researchers compared the ovarian cancer cells with the healthy cells of the fallopian tube. The researchers studied the differences in the metabolic processes of both types of cells using sugar. Through spectrometry results, they found that cancer cells preferred processing glucose (one form of sugar) through the citric acid cycle while the healthy cells favored the more common pathway called aerobic glycolysis.
These results showed that in high-grade serous ovarian cancer cells, the metabolic activity through the citric acid cycle would be higher. This observation means that targeting glycolysis activity will be ineffective in treating cancer cells. Moreover, this approach can be harmful to the survival of healthy cells.
Targeting the Key Enzymes of the Citric Acid Cycle
To better understand the metabolic process of cancer cells, the researchers studied the key enzyme of the citric acid cycle, isocitrate dehydrogenase 1 (IDH1). They blocked the normal or wild-type form of this enzyme and studied its effect on the tumor cells.
The researchers explored that IDH1 enzyme is highly expressed in both the primary (adherent) and metastasized (spheroid) HGSC tumor cells. As a result of its inhibition, cell division completely stopped, plus several genes turned off. The researchers wrote, "We found that wild-type isocitrate dehydrogenase I (IDH1) is the only TCA cycle enzyme upregulated in both adherent and spheroid conditions and is associated with reduced progression-free survival. IDH1 protein expression highly increased in patients with primary HGSC tumors. Pharmacologic inhibition or knockdown of IDH1 decreased proliferation of multiple HGSC cell lines by inducing senescence."
In high-grade serous cancer cells, the researchers have identified wild-type or non-mutant form of IDH1 enzyme.
Patients at Advanced Stages of Ovarian Cancer Can Also Benefit from this Treatment
Unfortunately, the diagnosis of ovarian cancer happens in most women when the cancer is spread to adjacent parts of the body as well. And the treatment options in later stages of the tumor are almost none.
However, this research has revealed that blocking IDH1 not only inhibits the progression of the primary tumor; instead, it also stops the cell cycle of the advanced ovarian cancer cells.
Several clinical studies have shown that when the levels of this enzyme are low in the body, ovarian cancer patients have longer survival time without tumor progression.
The US Food and Drug Administration (FDA) has previously approved for targeting the mutant form of this enzyme, IDH1. Now, the future objective is to use this already approved drug in the treatment of high-grade serous ovarian cancer. As Dr. Arid said, "One of our long term goals is to try and repurpose this already approved drug as a treatment for this form of ovarian cancer."
Future Perspective of this Treatment
In addition to using the existing FDA approved a drug to treat High-grade serous ovarian cancer type, the researchers intend to identify the prospects of combining IDH1 inhibiting medicines and other treatments. Further research in this regard can increase the progression-free survival of these cancer patients.
New Treatments for Ovarian Cancer are urgently required
Ovarian cancer is one of the leading causes of cancer-related deaths all around the globe. The chances of developing ovarian cancer in a woman's lifetime are around 1 in 78. And there are more than 90% chance of 5-year survival after a cancer diagnosis, only if cancer gets diagnosed at an early stage. As there are no particular symptoms or specific tests for tumor detection available, so early detection of ovarian cancer seldom happens. The diagnosis of this high-grade serous ovarian cancer is only possible when the tumor has spread and become spheroid.
With an immense difficulty in diagnosis, relapse of the tumor after chemotherapy, and shallow survival time, new treatment options for ovarian cancer and vast research in this regard can be helpful. This research has light up a new ray of hope for ovarian cancer patients.