05/10/2026
Finding a Cancer Mutation Does Not Mean the Targeted Drug Will Work
Precision oncology is becoming increasingly popular in veterinary medicine. By analyzing genetic changes in a tumor, genomic testing can identify mutations and suggest drugs designed to target them. But an important question remains: Does finding a mutation actually mean that a specific treatment will work?
A recent publication in Veterinary and Comparative Oncology raises important concerns about how genomic testing is being used to guide cancer treatment in dogs.
The presence of a mutation does not necessarily mean that the tumor depends on that mutation to survive or grow. Furthermore, the same genetic alteration may behave differently depending on the cancer type, tumor environment, and stage of disease. Identifying a molecular target is not the same as demonstrating that blocking it will improve treatment outcomes.
Experience in human oncology highlights these limitations. In the NCI MATCH trials, only 7 of the first 27 molecularly selected treatment groups met predefined criteria for a positive signal, with an overall objective response rate of just 10.3%. Although some targeted treatments showed meaningful activity, many molecular matches failed to produce the expected clinical benefit.
In veterinary oncology, the evidence is even more limited.
For example:
🔬 Mast cell tumors: Toceranib (Palladia) has demonstrated effectiveness against canine mast cell tumors. However, studies have failed to establish KIT mutation status as a reliable predictor of which dogs will respond to treatment.
🔬 Osteosarcoma: Despite strong laboratory evidence supporting inhibition of the mTOR pathway, a prospective randomized clinical trial involving 324 dogs found no survival benefit from adding sirolimus to standard therapy.
🔬 Urothelial carcinoma: BRAF targeted therapy with vemurafenib has produced responses in some dogs with BRAF mutations. However, responses were incomplete, treatment resistance developed, and predicting which dogs would benefit remained challenging.
These examples illustrate a critical distinction: A drug may have anticancer activity without a specific mutation reliably predicting its effectiveness.
Another important concern is that targeted treatments are not necessarily harmless. These drugs can produce adverse effects, interact with other medications, and create financial burdens. Using an unproven targeted treatment may also delay other therapies with stronger evidence of effectiveness.
This does not mean that genomic testing or targeted therapy should be abandoned. Both represent promising advances in veterinary oncology. However, identifying a mutation should often be considered a starting point for investigating potential treatments rather than proof that a particular drug will work.
The key message: Precision oncology should be guided by evidence of clinical benefit, not simply by finding a genetic match.
Larger, well designed, prospective clinical trials are essential to determine which molecular alterations truly predict treatment response and improve outcomes for dogs with cancer.
Precision-Guided Therapy for Canine Cancers: An Oasis or a Mirage?
https://onlinelibrary.wiley.com/doi/full/10.1111/vco.70119
