Research News

A postdoctoral researcher at Cleveland Clinic has created a new way to tell whether or not a patient with gynecologic cancer is likely to benefit from immune checkpoint inhibitors (ICIs). The Computers in Biology and Medicine study seeks to help physicians and patients make informed decisions about immunotherapy for ovarian, endometrial and cervical cancers. These cancers have long had low, unpredictable response rates. 

Gideon Idumah, PhD, led the study as part of his postdoctoral work in the laboratory of Ying Ni, PhD. Last year, he led a study that drew international attention for its potential to change how genetic testing is offered to healthy individuals concerned about their cancer risk. 

This new study extends genetic testing beyond risk assessment into treatment selection, especially for gynecologic cancer. 

“From day one, my goal has been to support Dr. Idumah’s growth as an independent scientist,” Dr. Ni says. “We helped him take on complex challenges and produce work with real potential to guide healthcare decisions on multiple levels.” 

Previous studies into genetics and metabolism had shown that a patient’s response to ICI therapy was not determined by any one factor. It was clear that the different factors influenced each other. So, to identify metabolic signatures associated with ICI success and failure, Dr. Idumah used systems biology to combine genetic and metabolic datasets with large‑scale modeling. This helped him see how our genes and metabolisms, and the tumor’s genes and metabolisms, influence each other. 

“ICIs have transformed treatment for many cancers, but only a small subset of gynecologic cancer patients benefit—and the treatment has side effects,” he says. “Understanding the mechanisms behind these differences gives us evidence for who will benefit from the treatment. This makes treatment more precise and effective.” 

Mapping metabolism as a predictor of immune checkpoint inhibitor response in gynecologic cancer 

Immune checkpoint inhibitors stop signals that keep our immune systems from attacking cancer cells. These drugs also help our immune cells recognize tumors as targets. 

Dr. Idumah believed changes in our metabolism could explain why ICIs work in some patients, but not others. 

“Metabolism isn’t just a bystander in cancer,” he explains. “It actively shapes how tumors respond to the immune system. And just as our metabolism affects a tumor, the tumor’s metabolism affects our healthy tissue.” 

It’s not always possible to directly measure metabolic changes in the clinic, so Dr. Idumah had to get creative if he wanted to find something physicians could use to help their patients.  

He partnered with gynecologic oncologist Haider Mahdi, MD, to analyze tumors from 49 women who received treatment for gynecologic cancer at Cleveland Clinic. He used a systems biology approach that combined genomic and metabolic data to build individual “genome-scale metabolic models.” Each model mapped the thousands of metabolic reactions encoded in a tumor’s DNA.  

This method helped Dr. Idumah find three different metabolic changes that consistently separated women who benefited from ICIs from those who did not. He could look at genetic testing to get a picture of the tumor’s metabolism, making the process simpler and more patient‑friendly.

A network of mentors driving network-based discovery 

Throughout the project, Dr. Idumah took on responsibilities that strengthened his independence as a researcher. He designed the experiments, analyzed the data and wrote the study manuscript—key skills for any postdoc preparing for the next stage of their career. He credits Cleveland Clinic with giving him the support system he needed to make important discoveries. 

“I’m grateful for the mentorship I’ve had here,” he says. “Dr. Ni has guided my development, and I've also learned from clinicians who collaborated with us. Having a network of mentors who are invested in my growth has made all the difference.”