Veterinary Blog

Medical Brief: Exceptional Responders in Veterinary Cancer

Dr Gerald Post
Dr Gerald Post
May 11, 2020
Forrest, an 11 year old Golden Retriever with hemophagocytic histiocytic sarcoma

Forrest, an 11 year old Golden Retriever with hemophagocytic histiocytic sarcoma

Patients are classified as exceptional responders if they achieve a complete or durable response after receiving a treatment in which fewer than 10 percent of patients have a complete or durable response to the same therapy.

In the past, these patients—human, canine or feline—would be classified as rare “medical miracles.” Now, with the advent of molecular and genomic diagnostics, these human patients are the subject of intense study, with the National Cancer Institute (NCI) and Harvard Medical School launching broad initiatives to evaluate the genetic keys that caused these patient’s tumors to be more responsive to therapy.

We at FidoCure® are extraordinarily interested in this approach and believe the evaluation of exceptional responders in veterinary oncology is an important area of research.

One of FidoCure's® First Cases: Forrest, an Exceptional Responder
One of the first pets to be enrolled in FidoCure®, Forrest, a 11 year-old Golden Retriever diagnosed with hemophagocytic histiocytic sarcoma, illustrates the value of this approach.

Traditional Chemotherapy and Targeted Therapy for Hemophagocytic Histiocytic Sarcoma
This extremely aggressive cancer typically has a median survival time of less than 2 months, even with surgery and traditional therapy. Forrest was still alive over 2 years post-diagnosis, clearly an exceptional responder. He was treated with surgery (splenectomy), traditional chemotherapy (lomustine), in conjunction with a targeted therapy, an HDAC inhibitor.   

Forrest's Tumor Had Mutation of the ATM Gene
Upon interrogation of the genomics of his tumor, a potential vitally important mutation was revealed. There was a mutation in the ATM (ataxia telangiectasia mutated kinase) gene and the ATM protein is majorly involved with DNA repair by activating enzymes that fix the broken strands.

DNA Damaging Therapies to HDAC Inhibition Sensitize Cancer Cells with ATM Mutation to DNA Damaging Therapies
Histone deacetylases (HDAC) play a major role in mitigating the response of the ATM pathway to DNA damage. HDAC inhibition decreases ATM activation and expression. In addition, HDAC inhibitors sensitize cancer cells to DNA damaging therapies. For example, lomustine chemotherapy alters chromatin structure and down-regulation of DNA repair.

The Genetic Mutation in Forrest's Tumor Might Be the Reason for His Exceptional Response

The next steps in the exceptional responder framework would be to further interrogate the mutation we found in the ATM gene.

We would recommend that dogs with the same ATM mutation in hemophagocytic histiocytic sarcoma receive the same treatment as Forrest, then monitor the patient's response. This is one way we can bring the true value of personalized medicine to our veterinary patients.

Incorporating the Exceptional Responder Framework Into Treatment Adds Value to Personalized Medicine

If you have any questions or comments about Forrest, exceptional responders, or hemophagocytic histiocytic sarcoma, please reach out
Dr Gerald Post