Personalized Veterinary Medicine: The future is now
By Kim Freeman, DVM, DACVIM (Oncology)
Veterinary Cancer & Surgery Specialists
firstname.lastname@example.org / www.vcsspdx.com
Personalized medicine has become quite the catch phrase these days in human medicine and especially cancer treatment. But what does it really mean? Does it mean that your doctor really gets to know who you are and spends more time with you discussing the nuances of your healthcare? Doubtful –But, it does mean new and more innovative ways of targeting disease. Personalized medicine is synonymous with genomic medicine. With the ability to unravel genomes has come the ability to identify the genetic makeup of disease. And when we can identify the genetic makeup or DNA “signature” of disease, we can theoretically customize medical care to the individual’s unique genetic makeup.
There are now drugs designed to target genes that cause disease. Pretty cool! This is the wave of the future for cancer therapy, since cancer is a disease of genetic mistakes. If we can unravel a tumor’s specific DNA to find a therapeutic target, then the success of therapy that addresses that specific target could improve dramatically over conventional chemotherapy, which is a more broad spectrum approach to inhibition of rapidly growing cells. For example, if you take 5 patients with a diagnosis of hemangiosarcoma that share similar characteristics on biopsy and look at the genomes of their tumors, you will find that these same 5 patients actually have very different tumors genetically. This helps explain why there is so much variability in outcomes and response to chemotherapy even for patients with the same diagnosis and biopsy characteristics. Some tumors may be more sensitive to the chemotherapy drugs whereas other tumors may be more resistant.
We can now test for this, which is so exciting! In veterinary medicine, we have seen examples of this type of tumor genetic testing in the last several years with the development of PCR for c-Kit mutations in canine mast cell tumors. Through PCR, we can identify exon 8 and exon 11 mutations within the c-Kit gene of canine mast cell tumors. This gene codes for tyrosine kinase,an “on/off” switch for many cell functions. In mast cell tumors, these c-Kit mutations can turn on tyrosine kinase to cause indefinite cell proliferation. In bedside terms, patients who carry these mutations are more likely to respond to a tyrosine kinase inhibitor (ex: toceranib or masitinib) than patients who do not carry these mutations.
In the future, we’ll be able to perform this type of genetic exploration on a much larger scale (i.e. genome wide) with other tumor types. VCSS is now working with a company called FidoCure which uses Next-Generation sequencing based assays and RNA diagnostics to identify changes in cancer related genes. Their assay can help confirm tumor types in situations where there is a “presumptive” diagnosis or a list of differentials that cannot be confirmed on histopathology alone — for instance, the assay can help differentiate between an oral fibrosarcoma and melanoma using genomic markers. FidoCure’s assay can be used to help assess potential response or resistance to chemotherapy, as well as to help identify potential small molecule inhibitor therapies for difficult cancers. These small molecule inhibitors may be especially beneficial for tumors that are inherently resistant to traditional chemotherapy or for patients that do not tolerate traditional chemotherapy. The hope is that these advances in science will translate to improved patient care and successful outcomes in our patient, and I am excited to have a new frontier to explore.
We have started using FidoCure for dogs with transitional cell carcinoma, a common cancer of the urinary bladder with limited treatment options. With a new urine test called a BRAF test, we can identify a specific cancer marker in a dog’s urine which can help inform which therapy to use. FidoCure offers access to a list of drugs that may be helpful for dogs with a positive BRAF urine test. Even though these drugs are today already used in people as targeted therapy,we have historically not had access to these options.
We also recently used FidoCure to help determine treatment for a patient with osteosarcoma of her skull. After collecting a surgical biopsy sample, we sent the sample out to the FidoCure lab for DNA sequencing and RNA expression. About 1 to 2 weeks later, we received results which FidoCure used to make list of treatment suggestions based on the gene expression profile. The oncologist then made a treatment recommendation based on this report. For this particular patient, FidoCure identified several targeted and conventional therapies that may be beneficial as well as noted some conventional drugs to which the patient may be resistant. This additional information is crucial when trying to make a successful treatment plan, and I look forward to being a part of the advancements we can make with personalized medicine.