Big Ideas

Andrea Bonetto, Ph.D.

While effective new therapies have markedly improved survival rates for many cancers, going through cancer treatment is still an exceptionally trying experience. In addition to the mental strain of facing a serious disease, the physical side effects from many cancer treatments can be excruciating, incapacitating and even deadly.

Andrea Bonetto, Ph.D., said he hopes his research will help patients avoid serious side effects and feel better while they are undergoing treatment.

With support from a 2017 V Scholar Grant from the V Foundation for Cancer Research, Bonetto and his team at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, are working to reduce the toll of common cancer therapies.

“A cancer diagnosis most often means having to face a long journey, which will be accompanied by moments of discomfort and pain, mainly because cancer therapies are directly responsible for severe side effects,” said Bonetto. “I am optimistic that someday cancer therapy will not necessarily mean all this! My research is aimed at isolating new mechanisms and factors, which can help identify new drugs to combine with chemotherapy regimens that are already in place.”

A critical need

Most who have been around someone undergoing cancer treatment has seen the muscle loss, weakness and general aching that often accompanies the process. Bonetto and his team are exploring ways cancer and cancer treatments often whittle away muscle mass and function, an effect known as cachexia, in hopes of finding ways to slow or stop it.

Cachexia poses a serious problem for cancer patients. Not only does muscle weakness make day-to-day life difficult, it can also become serious enough that it affects the ability to finish treatment. In fact, according to Bonetto, it is estimated that a third of cancer patients will eventually die from cachexia, not the cancer itself.

“Oncologists from all over the world recognize the importance of identifying new therapies to combine with routinely administered chemotherapy regimens for the purpose of reducing toxicities and improving quality of life and chance of survival in cancer patients,” said Bonetto.

A promising lead

Looking for leads, Bonetto’s team turned to a different medical condition altogether: osteoporosis. Osteoporosis is a common disease of aging that causes bones to become brittle and break easily. It is also, along with cachexia, a side effect of cisplatin, a chemotherapy drug used to treat ovarian and other types of cancer. Cisplatin is known to cause a loss of muscle mass and weakened muscles, as well as impacting bones by causing osteoporosis.

Bonetto’s idea was to see if osteoporosis medications known as bisphosphonates might be able to help cancer patients. In experiments using mice, they found combining cisplatin with bisphosphonates completely prevented the loss of bone that came with cisplatin being administered by itself. Even better, they found the combined therapy also had a positive impact on muscle mass and general strength.

While further research is needed to determine if the approach works in human patients, this was an exciting discovery for Bonetto, who said he hopes the new combination treatments will eventually be able to limit many of the debilitating side effects that make the road of a cancer journey so bumpy. Because bisphosphonates have already been tested and approved by the FDA, they could be approved for use alongside cancer treatments fairly quickly if clinical trials are successful.

“I hope that someday, thanks to my findings, cancer patients will not look at chemotherapy as something to fear, and will be able to face this moment with more serenity and optimism,” said Bonetto.