1
Personalized Medicine and the Future of Veterinary Cancer Care
C.KhannaDVM.PhD;DACVIM(Onc.);DACVP(Hon.), TheOncology Service, LLC
Personalized Medicine and The Future of Veterinary Oncology.
Chand Khanna DVM, PhD
Diplomate American College Veterinary Internal Medicine(Onc.)
Diplomate American College Veterinary Pathology(Hon.)
The Oncology Service LLC, Leesburg VA, Springfield VA, Richmond VA, and NW Wasington DC
A Perspective on curative outcomes for veterinary oncology.
A comittment to “delivering the future of veterinary cancer care”. Most notably, this future embraces an intent to cure. A historical perspective on the treatment of cancer has suggested that curative outcomes for patients with non-localized tumors are not possible and that a reasonable alternative is simple palliation of cancer in pets. This perspective is out of date and has been progressively replaced by one that recognizes that cures are possible today, and that improving cure rates is our collective goal. The development of novel treatments (and treatment modalities (i.e. Personalized Medicine, or stereotactic radiation therapy and the combination of multiple modalities of cancer treatment) now provide an increasing opportunity to realize this goal. The future of veterinary cancer care requires veterinary clinicians to discuss these new goals for cancer care and to use both existing and novel cancer therapies to discuss and deliver survivorship to our patients.
As our understanding of cancer biology expands and is translated to novel treatment approaches, significant improvement in long-term remissions and cures have been seen in cancer patients. This has come from early cancer detection and diagnosis, improved management of many of the previously dose-limiting toxicities related to cytotoxic drugs, and the development of new drugs.
Molecular biology meets the clinic.The completion and release of a publicly accessible draft of the canine genome and advances in our understanding of feline genomics have recently provided the opportunity to understand cancer in companion animals in similar ways to humans. The translation of this understanding of cancer biology has fueled drug and disease management strategies in humans, dogs and cats. Improvements in the treatments available to pets are and will be increasingly available through clinical trials
Personalized or Precision Medicine: In the setting of complex medical condition such as cancer, it is now reasonable and feasible to use molecular analyses to identify the true drivers of disease and to use correlative knowledge to link these drivers to specific treatments. Such an approach has been variably described as personalized medicine, precision medicine, or molecularly guided medicine. The use of the term Personalized medicine to describe this approach should not suggest that any past medical approaches were not precise or personalized. Rather, it should highlight the great degree of precision afforded by genomic analysis of individual patients, which complement existing clinical assessments of a patient’s individual disease presentation. This approach has received broad attention in both human and veterinary medicine as well as both the scientific and lay press. Indeed, recognition of precision medicine’s potential to transform patient outcomes has made its way into the field of presidential politics. It is increasingly the case that pet owners are aware and interested in the potential of these approaches to medicine being delivered to their pets, Accordingly a working knowledge of the field is now needed by the practicing veterinarian.
The goal of this session will be to provide the background needed to allow such discussions with clients and to allow informed decisions about pursuing personalized medicine as a treatment approach.
In human patients, precision medicine has seen its broadest application in the field of oncology. Despite the great need for improved outcomes in patients with cancer and the unquestioned value in defining cancer at its molecular level, many questions about the value of this approach remain unanswered and are not readily addressed in conventional preclinical models or human clinical trials. A primary problem has been a limited opportunity to test, optimize, and deliver evidence supporting improved patient outcomes with this approach. Rigorous study of each step in the delivery of precision medicine would most benefit from clinicians and experienced with patient to patient heterogeneity of complex medical problems like cancer and furthermore, the heterogeneity of cancer outcomes in a population. Through the unique training and perspective of veterinarians, the veterinary profession may address gaps in the understanding of evidence supporting precision medicine, in ways not possible in human paitients alone. The outcome of such leadership from the veterinary profession will be an accelerated understanding of the potential value of precision medicine for use in human patients and the commercial delivery of a precision medicine to veterinary patients.
Many ongoing prospective interventional clinical trials are now assessing the hypothesis that precision medicine can improve treatment outcomes in oncology. Results from the first such trial, published in 2010, report that treatment selection guided by personalized molecular profiling in refractory metastatic cancers resulted in longer progression-free survival in 27% of patients compared to progression during the patient’s prior regimen (13). Numerous observational and interventional trials have now been published or are ongoing and include adaptive trials such as I-SPY 2 in which treatment arms are adapted based on patient response, “basket” trials like the NCI MATCH trial in which patients with various advanced cancers are assigned to treatment baskets based on their tumor’s mutations, This same precision-guided scientific rationale is starting to be applied to clinical diagnosis and treatment of similar tumors bearing actionable mutations in dogs, although much remains to be learned about the molecular features underlying canine cancers (21, 22).
In time, the impact of precision medicine will have far reaching effects not only on cancer but on a variety of diseases including diabetes, obesity, infectious diseases, As a profession based on science and committed to improving animal and human health, veterinary medicine will utilize the same technological tools, scientific expertise, and social awareness now being pursued in human medicine to advance the clinical practice of precision medicine for the benefit of not only pets but humans and other species.