Bridging the Health Disparities Gap

Many health disparities across ethnic groups are predominantly caused by socioeconomic and environmental factors. But biological factors can also play a role. CCR researchers have identified several molecular features associated with aggressive and lethal prostate and breast cancers in African Americans — potentially creating opportunities for more targeted therapies and reduced health disparities.

One study, led by Senior Investigator Stefan Ambs, Ph.D., M.P.H., sought to better understand why African Americans disproportionately develop aggressive prostate cancer and are more likely to die from the disease compared to European Americans. To do so, Ambs and his team analyzed a large dataset that includes about 2,000 African American and European American men recruited primarily in and around Baltimore, Maryland, as well as a group of African men in Ghana. Whereas previous similar studies typically focused on analyzing tumor cells, Ambs’ team chose to analyze cancer-related immune signatures in the blood.

The results, published in Nature Communications, show a clear trend. Certain immune signatures associated with suppressed tumor immunity and more metastatic and lethal prostate cancers were found more frequently in Ghanaian and African American men compared to European American men. In particular, in African American men, two biomarkers, pleiotrophin, a pro-metastatic factor that regulates blood flow to tumors, and TNFRSF9, which regulates T cells, predicted poor disease survival among patients.

Ambs says these results suggest that African American men with suppressed systemic anti-tumor immunity might respond better to certain therapies that boost the immune system, and notes that other recent studies support this theory.

“We, as health disparity researchers, have really done something here in terms of helping clinicians tailor how they treat patients,” Ambs emphasizes. “Based on whether their patients have these biomarkers, clinicians might be able to decide if immunotherapy should be given or not.”

Several years ago, Ambs uncovered another health disparities pattern when he was sifting through a different dataset — this time related to breast cancer in African American women. He noticed increased RNA expression of a ubiquitin ligase, gp78, which helps to degrade proteins, in this population. To follow up on this finding, he alerted a CCR colleague, Senior Investigator Allan Weissman, M.D.

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Stefan Ambs, Ph.D., M.P.H.
Senior Investigator
Laboratory of Human Carcinogenesis

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Allan M. Weissman, M.D.
Senior Investigator
Cancer Innovation Laboratory

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Weissman has spent more than 20 years studying ubiquitin ligases and had previously shown that increased expression of gp78 promotes the formation of metastases in sarcoma. Weissman in turn teamed up with collaborator Kevin Gardner, M.D., Ph.D., now at Columbia University, New York, who had been diligently collecting tumor samples from more than 500 breast cancer patients in North Carolina.

Their analysis, published in JCI Insight, showed that increased protein expression of gp78 is independently associated with more aggressive disease and poor breast cancer survival in African American women.

Weissman says this finding could help clinicians better predict their patients’ prognoses, but also has broader therapeutic implications. “Knowing so much about the protein from our previous basic research provides opportunities to develop new strategies for more precise patient-specific breast cancer treatments.”

Health disparities research involves multi-faceted challenges and requires multi-faceted solutions. These studies are important first steps for understanding the molecular differences in tumor biology across diverse populations to help develop new therapies to close the health disparities gap.