Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer

Area of Science:

• Comparative oncology
• Gastrointestinal pathology
• Cancer genomics

Background:

• Spontaneous canine tumors are an underutilized cancer model.
• Colorectal cancer (CRC) research can benefit from comparative studies.
• Understanding tumor invasion patterns is crucial for effective subtyping.

Purpose of the Study:

• To compare proliferative and invasive canine colorectal tumors with human CRC.
• To identify molecular homology and shared pathogenic pathways.
• To refine human CRC subtyping based on canine tumor characteristics.

Main Methods:

• Global comparison of 20 canine colorectal tumors (proliferative vs. invasive).
• Molecular analysis of canine tumors for pathway activation and mutations (CTNNB1, TP53).
• Classification of 478 human colon cancers (The Cancer Genome Atlas) based on canine findings.

Main Results:

• Canine tumors show activated WNT/β-catenin and TP53 mutations.
• Three invasion patterns identified: collective, crypt-like, and epithelial-mesenchymal transition (EMT).
• Human CRC subtyping aligned with canine findings, suggesting further division of CMS4 into EMT and crypt-like subtypes.

Conclusions:

• Canine and human colorectal cancers share pathogenic pathways and invasion mechanisms.
• Dog-human integration refines CRC subtyping, particularly for mesenchymal subtypes.
• This comparative approach enhances understanding of colorectal cancer heterogeneity.