Improving immunotherapies for kidney cancer

(Press-News.org) A Medical University of South Carolina Hollings Cancer Center researcher is exploring new ways to improve treatment options for kidney cancer patients. With funding from a Department of Defense (DOD) Academy of Kidney Cancer Investigators Early Career Scholar Award, Aguirre de Cubas, Ph.D., will investigate how the immune system can be boosted to detect and kill kidney tumors. Congress established the award in 2017 to support research with high potential impact and exceptional scientific merit. De Cubas’ approach focuses on reactivating the immune system to recognize and target cancer cells better, offering new possibilities for improving existing therapies.

De Cubas studies renal cell carcinoma, the most common type of kidney cancer, which is often diagnosed at an advanced stage with poor prognosis. At diagnosis, 30% of patients have metastatic disease with a 5-year survival rate of only 12%. Immune checkpoint inhibitors have been a game-changer in cancer treatment, working by “removing the brakes” from the immune system to help it attack tumors. Unfortunately, response rates remain modest, with only about 1 in 5 patients with metastatic renal cell carcinoma experiencing lasting improvements.

To improve the detection of cancer cells by the immune system, de Cubas uses an innovative tool: mitochondrial DNA, or the genetic material inside the tiny powerhouses of our cells. When mitochondria are damaged, they can release DNA fragments into the cytoplasm in a way that is reminiscent of viral infection, alerting the immune system to danger. In many cancers, however, this alert system is disabled, leaving tumors undetected.

De Cubas uses strategies that mimic viral infection and trigger an immune response in cancer cells. One of these strategies involves targeting a BCL-XL protein to damage mitochondria, releasing mitochondrial DNA fragments that bring the alert system back online. His work aims to combine strategies activating viral mimicry with immune checkpoint inhibitors, making tumors more visible to the immune system and less resistant to treatment.

“Our ultimate goal is to develop a combination therapy that makes tumors more visible to the immune system while also removing its brakes so it can effectively attack the cancer,” he explained.

De Cubas credits the South Carolina Disparities Research Center (SC CADRE), a 13-year National Cancer Institute-funded partnership between MUSC Hollings Cancer Center and South Carolina State University (SCSU), a historically Black college/university, with helping him launch his research career and gather the preliminary data he needed to compete successfully for the DOD funding.

SC CADRE is co-directed by Marvella Ford, Ph.D., Endowed Chair, Cancer Disparities and associate director of Population Science and Community Outreach & Engagement at Hollings, and Judith Salley-Guydon, Ph.D., chair of the Department of Biological and Physical Sciences at SCSU. It aims to create a diverse future generation of cancer researchers specially trained to improve cancer health outcomes for South Carolinians by supporting emerging researchers like de Cubas.

“SC CADRE helped to bridge the beginning of my research ideas to a more mature concept,” de Cubas explained. “The program allowed me to develop new directions, collaborate with others and ultimately secure the funding to advance my work.”

De Cubas’ DOD award, which will enable him to establish his own independent laboratory, exemplifies the power of partnership in advancing cancer treatment and awareness. By connecting research expertise with community-focused initiatives, SC CADRE is shaping the future of cancer treatment and creating opportunities for a diverse generation of scientists.

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About MUSC Hollings Cancer Center

MUSC Hollings Cancer Center is South Carolina’s only National Cancer Institute-designated cancer center with the largest academic-based cancer research program in the state. With more than 150 faculty cancer scientists and 20 academic departments, it has an annual research funding portfolio of more than $50 million and sponsors more than 200 clinical trials across the state. Hollings offers state-of-the-art cancer screenings, diagnostic capabilities, therapies and surgical techniques within its multidisciplinary clinics to provide the full range of cancer care. Dedicated to preventing and reducing the cancer burden statewide, the Hollings Office of Community Outreach and Engagement works with community organizations to bring cancer education and prevention information to affected populations. For more information, visit hollingscancercenter.musc.edu.

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