Hollings researchers investigate potential new drug combinations against treatment-resistant forms of cancer

Researchers at MUSC Hollings Cancer Center are working to pursue better options for people with treatment-resistant cancer. They aim to develop new drug combinations, including eribulin mesylate, the active ingredient in the FDA-approved drug Halaven, and molecules under development at Hollings.

Mark Hamann, Ph.D., the Charles and Carol Cooper/SmartState Endowed Chair of Drug Discovery and Biomedical Sciences at the MUSC College of Pharmacy, is leading the effort for MUSC.

“The goal is to develop FDA-approved drug combinations that are more effective in treating cancer than either molecule on its own,” Hamann said.

Halaven is currently approved for patients with breast cancer that has metastasized, or spread, and isn’t responding to other chemotherapies. Eribulin is a microtubule inhibitor that binds to the ends of microtubules, which are structures that form inside cells and attach to chromosomes during cell division. Eribulin binding to microtubules inhibits their function during cell division, leading to cell death by apoptosis. Eisai Inc., the company that developed and manufactures eribulin, is providing it to MUSC under a Material Transfer Agreement, which enables MUSC to complete this research.

“Eribulin is considered an appropriate treatment for metastatic triple-negative breast cancer,” Hamann said. “But it's still not a cure. And, of course, there are still side effects.”

The most effective treatments for cancer typically involve multiple approaches or drug combinations. Drug combinations can work together to target different weaknesses, leading to the ultimate goal of remission.

Hamann said MUSC researchers have about half a dozen unique molecules that interact with different targets and may effectively synergize with eribulin. Success in the lab could pave the way for clinical trials and later-stage development of the combinations for the market.

“We feel confident that at least one new class of chemotherapeutic agents that we have in hand may work well due to promising activity with another class of microtubule inhibitors in preclinical models,” Hamann said.

Many of MUSC’s molecules, like Eisai’s eribulin, are derived from natural products. Eribulin is a synthetic analog of halichondrin B, a natural product originally discovered from the sea sponge Halichondria okadai.

“Most of our molecules are derived from a natural product source or modified from a natural product source. And many of them are sponge-derived metabolites,” Hamann said, adding that this work highlights MUSC’s strengths in natural product discovery and drug development.

MUSC has a pipeline of natural products in various stages of development. Some have been tested in mouse models, and others have completed clinical studies. Nancy Klauber DeMore, M.D., has completed a phase 1a clinical trial of an extract from Boswellia, the plant that produces frankincense, in breast cancer patients. Although the active pharmaceutical ingredients in Boswellia extract still must be fully mapped out to meet FDA requirements, MUSC researchers believe they would be excellent candidates for these types of combination studies.

Other molecules of interest are being studied in the labs of John O’Bryan, Ph.D., Aaron Hobbs, Ph.D., and George Hanna, Ph.D. They and their labs will likely be involved in assessing how well the different combinations work.

If these combinations work in preclinical models, they will then need to be tested through clinical trials. The ultimate goal, Hamann noted, is that one or more of these potential new combinations would improve outcomes for patients, giving people more quality time with their loved ones.

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