HER2 Expression in African American Men with Prostate Cancer
Abstract
African American men are much more likely to be diagnosed with prostate cancer and die from the disease than any other race/ethnicity in the United States. There are multiple reasons for this glaring disparity, including socioeconomic, environmental, biological, and genetic factors. A disturbing trend observed in the clinic is the tendency for African American men to be diagnosed at an advanced stage of prostate cancer. This is problematic as prostate cancer is nearly 100% curable if detected early—according to the American Cancer Society—but only 31% curable if discovered in later stages. Many times, men suffer no symptoms until later stages, and recent studies associate delayed prostate cancer screening to increasing prevalence of late-stage diagnosis. To further complicate the issue, at the time when African American men are diagnosed, the biological characteristics of their tumors are worse. Scientists concerned with discovering the underlying factors that drive aggressive tumors at the cellular level have detected specific genes that trigger cancer cells to divide more quickly and spread throughout the body. HER2 is one such gene. Because HER2-positive cancer cells exist in many breast cancer patients, HER2-targeted drugs that kill those cancer cells specifically have been used with much success for many women. However, the role of HER2 in prostate cancer patients has not been fully explored. A decade ago, a few clinical trials were developed to treat prostate cancer patients with HER2-targeted drugs. However, the trials were ended because (1) most patients did not have HER2 positive tumors and (2) the HER2-targeted drugs available at the time were ineffective. Unfortunately, the trials did not report on the race of the patients. However, in a troubling pattern often repeated in biomedical research, we know that African American men are rarely included in pivotal drug treatment studies. In preliminary experiments conducted over the past few months, our team observed that African American prostate cancer tumors express HER2. Furthermore, after analyzing the DNA ancestry of the men, we observed that African American men with higher West African ancestry were more likely to have HER2 positive tumors. Because of the transatlantic slave trade routes, DNA passed down throughout African American generations originated in West Africa and is preserved within individuals in varying proportions. Therefore, when conducting research using African American biospecimens, it is imperative to tease out accurate genetic ancestry to optimize gene-targeted treatment options. In my research proposal, I believe that increasing the number of African American biospecimens and patients in the study will confirm what we have observed in a small subset of patients—that (1) African American prostate cancer patients are more likely to have HER2 positive tumors, (2) increased HER2 expression triggers cancer cell growth and spread, and (3) HER2 expression can be linked to advanced disease stage, worse clinical features, worse response to standard prostate cancer treatment, and shorter survival. The implications of successful completion of this study cannot be understated. If I can establish that African American men with prostate cancer are more likely to have HER2 positive tumors, then there is a tremendous potential to treat—if not cure—these patients with new-generation HER2-targeted drugs that are currently improving survival for women with HER2 positive breast cancer. In addition, there is further incentive to complete this study, as recent reports have revealed that African American men respond better to treatment and survive longer than others when offered identical prostate cancer drug treatments. Given the strong collaborations we have established with leading clinicians who design prostate cancer clinical trials and treat patients at the City of Hope Comprehensive Cancer Center, the ability to provide HER2-targ
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110038
Entities
People
- Leanne Burnham
Organizations
- Beckman Research Institute of City of Hope
- United States Army