Release Date: April 27, 2022
BUFFALO, N.Y. – The University at Buffalo has received a $2.3 million grant from the National Cancer Institute to identify metabolic vulnerabilities of ovarian cancer and to develop potential treatments for the disease.
The research, led by Sukyung Woo, PhD, associate professor of pharmaceutical sciences in the UB School of Pharmacy and Pharmaceutical Sciences, aims to fast-track the development of drugs that target apelin – a peptide that when expressed within body fat helps ovarian cancer cells better consume lipids – and the apelin receptor (APJ) by utilizing a combined experimental and computational mathematical modeling approach.
High-grade serous ovarian cancer is the most common and malignant form of ovarian cancer, accounting for nearly 80% of ovarian cancer deaths, says Woo. The high mortality rate is largely due to most patients being diagnosed with advanced-stage disease when tumors are widely metastasized and have developed drug resistance, she adds.
Unlike most other cancers, ovarian cancer cells primarily metastasize within the abdomen, preferably in lipid-rich areas such as the omentum. Ovarian cancer cells rely on lipids as an energy source for survival, spread and drug resistance.
“By completing these studies, we will establish the importance of apelin and APJ as a therapeutic target in ovarian cancer – a malignancy for which effective therapies are desperately needed to improve patient outcomes,” said Woo.
The investigators will also explore the significance of ovarian cancer cells’ capacity to form cell clusters called spheroids, which travel through bodily fluids to reach new sites within the abdomen.
APJ promotes the spread and chemoresistance of ovarian cancer cells by regulating their capacity to form spheroids and their metabolic switch to using lipids as energy, and by supporting the formation of new blood vessels through a process called angiogenesis, says Woo.
Previous studies led by Woo have found that greater expression of apelin and APJ within tumor microenvironments resulted in increased use of lipids as energy by ovarian cancer cells, leading to better survival, fitness and spread of the cells.
The findings also demonstrated that blocking the APJ pathway is possible, reducing the risk of cancer spread and improving the effectiveness of chemotherapy targeted at ovarian cancer, says Woo.