BME’s Thai Thayumanavan Collaborates with Researchers at UMass Chan Medical School on Pioneering Cancer Paper

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Ferroptosis is a form of regulated cell death caused by a toxic-iron buildup of lipid peroxides in cell membranes. In that context, many researchers are trying to understand the role of ferroptosis in cancer and exploit it to improve cancer therapy. Now, Thai Thayumanavan, the head of the UMass Amherst Biomedical Engineering (BME) Department and a Distinguished Professor in the BME and Chemistry (UMass Chem) departments, has collaborated with 11 researchers from UMass Chem and the University of Massachusetts Chan Medical School (UMass Med) to publish a groundbreaking paper on ferroptosis in Cell Chemical Biology. 

Thayumanavan and his research group members has collaborated with Professor Art Mercurio of the Department of Molecular, Cell, and Cancer Biology at UMass Chan Medical School and his research group members. 

According to Thayumanavan, “This is an awesome example of a collaborative work between UMass Med and UMass Amherst.” 

How is ferroptosis being studied to treat cancer? According to the University of Texas MD Anderson Cancer Center, “Scientists have designed and identified various compounds called ferroptosis inducers. They are capable of disabling ferroptosis defense systems and triggering cells to undergo ferroptosis.” Hence, cancer studies on ferroptosis focus on combining ferroptosis inducers with standard treatments such as chemotherapy and radiation therapy to make cancer treatments as effective as possible.

As the Cell Chemical Biology paper explains about employing ferroptosis in cancer treatment, “This therapeutic approach is particularly attractive because more aggressive tumor cells, including cells that persist after standard-of-care therapy, are more vulnerable to ferroptosis than other tumor-cell populations. This approach, however, is challenged by the emerging role of ferroptosis in various physiological processes such as aging and development. This issue creates concerns over systemic administration of ferroptosis inducers for cancer therapy because of possible significant side effects.” 

In response to this challenge, as the Cell Chemical Biology paper says, the authors are carrying out cutting-edge research “to gain insights into the molecular basis of ferroptosis sensitivity in the context of tumor-cell phenotype.” One mission of the research is to use ferroptosis to target cancer tumors very specifically, suppress the cancer, reduce drug dosage, and improve therapy while also avoiding any negative side effects. 

In the project described by the Cell Chemical Biology paper, the researchers have been leveraging a newfound role for a protein called PD-L1 to induce ferroptosis, which is previously most known for its role in immune suppression for cancer cells to evade the immune system. 

As the paper explains, “We synthesized an antibody nanogel conjugate (ANC), comprised of an anti-PD-L1 antibody conjugated to a nanogel encapsulated with imidazole ketone erastin (IKE), a ferroptosis inducer. This ANC targets PD-L1-expressing cells in vitro and in vivo and induces ferroptosis, resulting in tumor suppression.”

The Cell Chemical Biology paper concludes that “Importantly, this approach is superior to systemic administration of IKE because it enables enhanced delivery of IKE specifically to tumor cells and it requires lower drug doses for efficacy.”

This project was executed through a close collaboration between the co-first authors Mengdie Wang (UMass Med) and Theo Prachyathipaskul (UMass Chem) and Mengdie Wang (UMass Med) from the Mercurio and Thayumanavan research groups respectively. This project was supported by the National Institutes of Health grants, a Department of Defense grant and a Royal Thai Scholarship from the Development and Promotion of Science and Technology Talents Project in Thailand to Prachyathipsakul. (December 2024)