Molecular differences in pancreatic cancer of patients with Caucasian or African Ethnicity

Last Updated on April 6, 2025 by Joseph Gut – thasso

April 05, 2025 – Researchers have discovered race-associated molecular differences in tumors that may impact the way patients with pancreatic cancer respond to immunotherapies. The findings, which were recently published in the journal Cancer Research Communications, reinforce the need to include ethnically/racially diverse participants in clinical studies.

Immunotherapies are a type of cancer treatment that uses the body’s own immune system to fight cancer. Patients of African ethnicity (in the US reffered to as African American patients)  have a higher incidence of pancreatic cancer, the third leading cause of cancer-related death in the United States, compared with other ethnical/racial groups.

In the article appearing in the AACR Journal, researchers at the Henry Ford Health Pancreatic Cancer Center, found that African American  patients showed a higher prevalence of PD-L1 overexpression, a marker often linked with aggressive cancer behavior and a key target for immunotherapy treatments. Additionally, African American patients showed higher frequencies of TP53 mutations and KRASG12R mutations compared to white patients. Those genes affect how quickly cancer grows and the body’s ability to fight cancer.

“This finding strongly supports that in clinical trials across the country, we need to enroll patients from different ethnic/racial groups to reflect the racial makeup in the U.S. and to more accurately represent tumor molecular changes,” said lead researcher Ling Huang, Ph.D. In a separate analysis of recent clinical trials testing immunotherapies for pancreatic cancer, the researchers found that African American patients and other minorities were underrepresented in most clinical trials. “It is also important to ensure people of different ethnic/racial background have equal access to cancer care, especially precision medicine,” Dr. Huang said.

PD-L1 is like a shield that some cells wear. Normally, it tells the immune system’s T cells (which kill harmful cells) not to attack. Cancer cells can hijack this signal, wearing 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 harder for the body to fight the cancer, leading to a worse outlook for the patient.

Think of TP53 like a brake pedal in a car that helps stop cancer growth. If something goes wrong with this gene (like mutations), it’s like the brakes are broken, and the car (or cancer) can keep going without control.

The KRAS gene is often faulty in pancreatic cancer. The KRASG12R is a specific error in this gene. This error makes the KRAS gene stuck in the “on” position, constantly telling cells to grow and divide, which can lead to cancer. This is like flooring the gas pedal of a car, making it accelerate to full speed.

This study shows that, in pancreatic cancer, African American patients tend to have higher levels of the PD-L1 shield on their cancer cells compared to white patients. This could affect how their cancer progresses and responds to treatment.

The research team emphasizes that these molecular features are not necessarily the determinants, but associations that help understand the complex nature of cancer disparities. “We hope that these insights will guide future studies and lead to improved outcomes for all patients, regardless of ethnicity/race,” Dr. Huang said.

Molecular profiles of patient tumors were determined from the Tempus multimodal database, through collaboration between Dr. Huang’s team, Tempus AI, and Henry Ford scientists, Howard Crawford and Albert Levin. Members from Dr. Huang’s team, Saurabh Mandal and Swathi Sridhar also contributed significantly to this project.

Based in Detroit, where 77% of the population identifies as African American, Henry Ford Health is nationally recognized for its commitment to inclusive research endeavors that address health care disparities, develop new treatments, and identify ways to prevent and understand disease.

Thasso has addressed in the past in several posts here, here, here, here, and here, just to list a few, the variations and difficulties in the adequate representation of patients with African ancestry / ethnicity in modern medical research and development of genetics-based therapies.

See here a short sequence on pancreatic cancer in patient of African ethnicity:

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