HMN 2026: how ovarian cancer resists chemotherapy—and how to reverse it

Michigan State University researchers have identified how ovarian cancer cells become resistant to chemotherapy and discovered a protein that, when blocked, can restore the drug’s effectiveness.

The findings, published in Cell Reports, center on cisplatin, a widely used chemotherapy drug first discovered at MSU in 1965 and still considered among the gold standards for treating ovarian and other cancers.

It’s long been understood that cisplatin works by damaging cancer cells’ DNA, but this study shows that it also disrupts microtubules, which are the internal scaffolding cells rely on to survive.

“We have learned how cancer cells adapt to chemotherapy by altering their internal structure,” said Sachi Horibata, 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. “This enables them to survive and ultimately resist treatment.”

TPPP3 helps tumors endure treatment

At the center of that process is a protein called tubulin polymerization promoting protein 3, or TPPP3. The researchers found that cancer cells with higher levels of TPPP3 were better able to stabilize their internal scaffolding and withstand the effects of cisplatin or carboplatin, which tries to destroy that internal scaffold.

In contrast, patients with lower levels of TPPP3 lived longer and responded better to treatment. In laboratory models, removing the protein significantly restored cancer cells’ sensitivity to cisplatin, suggesting a new approach to overcoming resistance.

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

A personal drive behind the work

The discovery also helps explain why some patients are told they are cancer-free, only to see the disease return.

After her grandmother was diagnosed with ovarian cancer, Horibata made it her life’s work to understand that pattern—why tumors initially respond to treatment but later come back stronger.

This research shows progress in her quest. Rather than simply repairing DNA damage, cancer cells can reprogram what scientists call the “tubulin code”—a set of structural changes that help stabilize microtubules and support survival under stress.

By shifting focus beyond DNA to the physical structure of cancer cells, researchers say the findings could open the door to improving existing treatments rather than replacing them.

From lab finding to treatment strategy

Researchers are now working to translate these findings into new treatment strategies, including developing drugs that target TPPP3 and testing whether the protein can be used as a biomarker to identify patients at risk of developing resistance.

Future studies will also examine how this mechanism affects current chemotherapy combinations and whether it plays a role in other cancer types.

“This is about staying one step ahead of cancer,” Horibata said. “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.”

The findings may also have broader implications. 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.

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