Michigan State researchers identify protein tied to ovarian cancer chemo resistance

Researchers at Michigan State University say they may have found a way to stop ovarian cancer cells from resisting chemotherapy and make those same cells sensitive to treatment once again.

The study centers on a protein called tubulin polymerization promoting protein 3, better known as TPPP3. But this isn't a protein that patients need more of, it's actually quite the opposite. Patients with tumors that had lower levels of TPPP3 responded better to treatment and laboratory models showed removing TPPP3 completely restored sensitivity to the drug cisplatin. Cisplatin is often used to treat ovarian cancer.

"We have learned how cancer cells adapt to chemotherapy by altering their internal structure," Sachi Horibata, assistant professor at the MSU College of Human Medicine, said in a statement. "This enables them to survive and ultimately resist treatment."

Horibata is an assistant professor in the Precision Health Program and Department of Pharmacology and Toxicology at the MSU College of Human Medicine and one of the lead researchers on the study.

"TPPP3 acts like a protective shield for cancer cells," Horibata continued. "When we remove it, we weaken the cell's defenses and allow chemotherapy to work more effectively."

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Another focal point of the research is small structures inside cancer cells called microtubules. Think of them as support structures that give cells their shape, move materials and help them divide. Microtubules are made from the protein tubulin. The term "tubulin code" is often used to describe chemical changes to tubulin that affect the behavior of the support structure. In simple terms, the tubulin code helps tell cells whether their internal framework should be flexible, unstable or reinforced.

According to MSU's findings, ovarian cancer cells that are resistant to chemotherapy can change the inner support structure framework. The cells, outside of only being repaired by damage caused by chemotherapy, the cells do show signs of strengthening their microtubules by assisting them in surviving the stress of treatment.

This is where the TPPP3 protein comes into play.

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"The findings may also have broader implications," the university writes. "Because microtubules are essential in many healthy cells, this research could help scientists better understand some of chemotherapy's most common side effects, including nerve damage, hair loss and hearing loss."

"This is about staying one step ahead of cancer," Horibata added. "If scientists can understand how tumors adapt to survive treatment, we can start to block that process - making existing therapies more effective, more durable and ultimately more personalized for each patient."

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