A Genetic Mutation May Have Increased Human Vulnerability to Cancer Compared to Chimpanzees

Recent research from UC Davis Comprehensive Cancer Center has identified an evolutionary genetic change that could explain why humans might be more susceptible to certain cancers than our closest primate relatives, like chimpanzees. The study highlights a specific mutation in an immune system protein, Fas Ligand (FasL), which appears to undermine immune defense against solid tumors.

The investigation, published in Nature Communications, focused on a single amino acid variation in the FasL protein. While in non-human primates this protein remains resistant to enzymatic breakdown, in humans a substitution of serine for proline at position 153 makes FasL more vulnerable to degradation by plasmin — an enzyme associated with tumor progression.

This mutation likely played a role in human evolution, possibly contributing to our larger brain size, as suggested by senior author Jogender Tushir-Singh. However, it has a downside in the context of cancer: the tumor-associated enzyme plasmin can disable FasL, preventing immune cells from executing apoptosis — a programmed cell death crucial for eliminating cancer cells.

In tumors like ovarian, colon, and triple-negative breast cancers, plasmin levels tend to be elevated, especially in aggressive solid tumors. This enzyme cleaves FasL, diminishing its capacity to signal immune cells to kill cancer cells, thus weakening immune responses and reducing the effectiveness of therapies like CAR-T and T-cell therapies.

Encouragingly, the research also shows that inhibiting plasmin or protecting FasL from cleavage can restore its ability to fight cancer. Such strategies could enhance current immunotherapy approaches for difficult-to-treat solid tumors. Understanding this genetic trade-off not only sheds light on human cancer susceptibility but also opens new avenues for personalized, targeted treatments.

This discovery underscores the importance of evolutionary biology in understanding disease mechanisms and highlights potential new therapeutic targets to improve cancer treatment outcomes in humans. For more detailed information, see the original study at [https://doi.org/10.1038/s41467-025-60990-0].

Source: https://medicalxpress.com/news/2025-07-genetic-mutation-humans-vulnerable-cancer.html