Investigators studied race-associated molecular differences in the pancreatic tumors of Black and White patients to determine whether such differences were associated with response to immunotherapy. The findings were published recently by Mandal et al in Cancer Research Communications and reinforce the need to include racially diverse participants in clinical studies.
Background
The TP53 gene is capable of stopping cancer growth. The KRAS gene is often faulty in pancreatic cancer, and KRAS G12R is a specific mutation that can lead to cancer. Both of these genes affect how quickly cancer grows as well as the immune system's ability to fight cancer.
PD-L1 acts like a shield for some cells. Typically, it tells the immune system’s T cells not to attack. However, cancer cells can hijack this signal and use PD-L1 as armor to protect themselves from being destroyed by the immune system. When cancer cells have a lot of this PD-L1 shield, it’s often challenging for the body to fight the cancer, leading to poorer patient outcomes. PD-L1 overexpression is a known marker linked to aggressive cancer behavior and a key target for immunotherapy treatments.
Compared with other racial groups, Black patients have a higher incidence of pancreatic cancer, the third leading cause of cancer-related mortality in the United States.
Study Methods and Results
In the study, the investigators used the Tempus multimodal database to determine the molecular profiles of pancreatic tumors in Black and White patients.
The investigators found that in Black patients, tumors exhibited a higher prevalence of PD-L1 overexpression and higher frequencies of TP53 mutations and KRAS G12R mutations compared with tumors in White patients. This could affect how cancer progresses and responds to treatment. The investigators stressed that these molecular features are not necessarily the determinants, but associations, that help portray the complex nature of cancer disparities.
“This finding strongly supports that in clinical trials across the country, we need to enroll patients from different racial groups to reflect the racial makeup in the [United States] and to more accurately represent tumor molecular changes,” emphasized senior study author Ling Huang, PhD, of the Henry Ford Health Pancreatic Cancer Center.
In a separate analysis, the investigators discovered that Black patients and other racial minorities were underrepresented in a majority of recent clinical trials exploring immunotherapies in patients with pancreatic cancer.
Conclusions
“It is … important to ensure [patients] of different racial backgrounds have equal access to cancer care, especially precision medicine,” Dr. Huang emphasized. “We hope that these insights will guide future studies and lead to improved outcomes for all patients, regardless of race,” he concluded.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.
