Cancer disparities present a significant public health challenge, as differences in prevention, screening, and treatment contribute to varied cancer incidence and mortality across populations. Socioeconomic status, access to healthcare, and environmental exposures are critical factors, but genetic variations among diverse populations also contribute significantly (Fig. 1). Most cancer research focuses on populations of European ancestry, and many new cancer technologies are not tested in diverse groups, limiting their applicability and leaving efforts to reduce inequities inadequate.
Diversity in Cancer-Associated Mutations
Cancer-associated mutations occur at different rates across ethnic and racial groups.
For example, BRCA1 and BRCA2 mutations, which increase the risk of breast, ovarian, prostate, and pancreatic cancers, occur in 0.2–0.3% of the general population but are ten times more common (2%) among Ashkenazi Jews [2]. Also, African Americans carry distinct BRCA1 variants that are not present in other racial or ethnic groups in the U.S. [3].
Overall, Black individuals have more frequent TP53 and KRAS mutations in primary breast and prostate cancer, respectively, compared to White patients, while EGFR and FOXA1 mutations are more common in Asian patients in lung and prostate cancer, respectively (Fig.2) [4] [5].
Yet, cancer research and clinical trials often lack adequate representation of this diversity, leading to delayed diagnoses, inequitable access to treatments, and limited progress in developing targeted therapies [6].
Canine Cancer Models
Canine cancer models offer a unique opportunity to advance research and address health inequities due to their significant biological and molecular similarities to human cancers, as well as their shared environmental exposures. With a high incidence rate of spontaneous tumors, immunocompetency, and mutations similar to those found in humans, dogs provide a more accurate model for human cancer development and prognosis. Canine cancers also progress more rapidly, making them an ideal model for testing new therapies in a treatment setting. This genetically and environmentally diverse model allows for more targeted studies of different cancer types, further enhancing our understanding and improving treatment options [8].
In comparison, while rodent models are highly informative for early-stage research, their success rate in drug development is relatively low (~11%) due to differences in tumor complexity and immune system responses [9] [10] [11].
Dogs, living in household environments alongside humans, are exposed to similar environmental factors such as air pollution and diet, which influence their genome, epigenome, microbiome, and metabolome. This makes canine models especially valuable for longitudinal studies on how these exposures impact cancer development [9]. Furthermore, dogs have immune cell profiles similar to humans, making them ideal candidates for immuno-oncology research [8] [11].
With mutations linked more to tumor type than breed [12], the prevalence of certain tumor types in different breeds [13] enables targeted studies for specific subtypes of cancer. For example, Golden Retrievers are highly susceptible to lymphoma and hemangiosarcoma [14], while Scottish Terriers are more prone to bladder cancer [15].
The value of canine models is particularly evident in pediatric cancer research. Pediatric cancers often differ in molecular profiles from adult cancers, presenting a challenge for developing effective treatments [17]. Canine models, especially those that develop gliomas and osteosarcomas, offer insights that are more relevant to pediatric cancers than traditional models. For example, canine gliomas share DNA methylation patterns and genetic profiles with human pediatric gliomas [18]. Similarly, canine osteosarcoma exhibits mutations found only in pediatric osteosarcoma, providing a more accurate comparative model than adult osteosarcoma models [19]. This makes canine models a crucial tool for advancing pediatric cancer research and improving treatment strategies.
Despite the many advantages of canine cancer models for diagnostic and therapeutic research, several challenges remain. For example, the number of sequenced canine tumors is much smaller compared to human tumors, limiting the depth of understanding regarding actionable mutations in dogs. However, platforms such as FidoCure are helping to bridge this gap between canine and human cancer research. FidoCure is an AI-driven precision medicine platform designed to bring cutting-edge cancer treatments, such as targeted therapies, to dogs. While its primary focus is veterinary oncology, the platform also contributes to linking canine genetic data to human oncology research, accelerating drug discovery and enhance precision medicine for both species [20].
In conclusion, canine cancer models provide a powerful tool for addressing health inequities in cancer research. By studying naturally occurring tumors in dogs, scientists can gain valuable insights that improve treatment diversity and develop more inclusive therapies.