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Keywords: testicular cancer, therapy, drug targets
Testicular cancer is the most common cancer in young males ages 15 to 35. The most conventional chemotherapy drug used to treat this is called cisplatin, but it is toxic and comes with many negative side effects including hearing loss, and kidney and nerve damage. There is a lack of effective drugs for patients who are resistant to the standard therapy, but a new option arises.
Cancer Center at Illinois (CCIL) member Michael Spinella and his lab are investigating a new approach for killing tumor cells with epigenetic drugs, or “epidrugs,” that target the polycomb pathway. Doha Shokry and Ratnakar Singh contributed as the first and last authors of this work.
“It’s a very unique disease because it’s one of the few types of cancers that can be cured with conventional chemotherapy, but no one really knows why. Certain patients become resistant to the therapy, and no one knows why either,” said Spinella. The lab’s goal is to figure out ways to overcome that resistance and come up with other therapies for those patients.
“Our hypothesis was that if we target a specific epigenetic pathway in the cells called the polycomb pathway, that we could treat testicular cancer cells and tumors,” said Spinella. Testicular cancer, unlike most cancers, is driven by epigenetic mechanisms. This is why the team was inspired to use this class of drugs, which they found works for testicular cancer resistance to the standard therapy.
Left to right: Ratnakar Singh, Cancer Center at Illinois (CCIL) member Michael Spinella, and Doha Shokry
“When we did the experiments in vitro in cell culture, we saw a modest response. But what really surprised us is when we looked at it in mice, the response was really dramatic,” said Spinella. When treated with cisplatin, the mice responded partially. However, when treated with the new epigenetic drug, the mice’s cancer completely disappeared.
The team’s next steps are testing in different mouse models, and then eventually moving forward to clinical trials on humans, focusing on patients who have failed in all other therapies. The mortality rate is very high for these patients, but this new therapy will give them a chance to try something else.
For patients who respond to cisplatin, this therapy might work in tandem with it to decrease the harmful effects. “What we’re hoping is that eventually our approach might be able to decrease the amount of cisplatin these patients are seeing so they’ll also have less side effects,” said Spinella.
Editor’s notes:
Michael Spinella is a Professor of Comparative Biosciences. Spinella is also an affiliate of the University of Illinois College of Veterinary Medicine. He can be reached at spinella@illinois.edu.
This research is reported in the paper “Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B” and is available online.
https://doi.org/10.1186/s12964-024-01912-3
This story was written by Florence Lin, CCIL Communications Intern.