LITMIR.BIZ

2.20 Cancer Precision Medicine

       Anna Katogiritis, BSc, DVM1 and Chand Khanna, DVM, PhD, DACVIM (Onc), DACVP (Hon)2

       1 I ndependent SA and Wildlife Emergency Veterinarian and NGO Consultant, USA

       2 Ethos Veterinary Health, Woburn, MA, USA

BASICS

      2.20.1 Summary

      Cancer is a disease of dysregulated genes. Personalized cancer medicine (Pmed) is a therapeutic approach to pet‐specific care that most often analyzes the molecular features of a patient's cancer, and uses this information to design treatment plans that target critical genetic alterations in that patient's tumor. In so doing, this field hopes to select approaches that may more specifically target cancer cells. This approach may also allow rapid alterations in treatment in response to patient‐specific drug resistance signals that emerge during therapy and individualize monitoring of therapeutic responses. It is nearly certain that aspects of this overriding Pmed approach represent the future of cancer medicine.

      2.20.2 Terms Defined

      Genome: This term refers to an organism's complete sequence of DNA.

      Genomics: A field of molecular biology that focuses on the structure, function, mapping, and evolution of the genome.

      Mutations: Permanent alterations in the DNA sequence. These can occur due to mistakes that arise during the DNA replication process, environmental factors (e.g., ultraviolet light), or infections (e.g., viruses).

      Precision Cancer Medicine: An emerging field in oncology and molecular biology through which a patient's cancer is analyzed to a molecular level with the goal of identifying unique characteristics (most often specific mutations) that may respond more favorably to specific (targeted) treatments.

MAIN CONCEPTS

      2.20.3 Cancer is a Disease of Dysregulated Genes

      It is clear that cancer is a disease of dysregulated genomics. New genomic characterizations of cancer (combined with dramatic reductions in the cost of genomic analysis and computing power, and the parallel genomic and biological annotation, i.e., “naming,” of cancer‐associated genes) has fueled the field of precision medicine as a therapeutic approach, delivered recent drug approvals in human oncology, and is increasingly available to all species of cancer patients.

      2.20.3.1 Precision Medicine for Oncology

      In many disease conditions, it is well understood that conventional methods of disease characterization are insufficient to fully inform clinicians of an individual patient's needs. For the most part, the genomic characterization of many disease states can better account for these needs. As such, Pmed can allow clinicians to select better initial approaches to therapy, more rapidly alter treatment approach, and individualize plans for disease monitoring. From the perspective of need and opportunity, the field of oncology is most ready and in need of this evolution in medicine. Collectively, this has created the opportunity for relatively inexpensive genomic and molecular characterizations of disease states.

      2.20.4 Cancer Precision Medicine for Individualized and Molecular Therapy

      In the delivery of Pmed, a tissue biopsy or blood sample (liquid biopsy) from the patient will be used to extract nucleic acids for genomic sequencing. Altered genes are prioritized as therapeutic targets. These are then matched with specific drugs that inhibit the altered gene or its pathway. An individualized cocktail of therapeutics, matched to the patient's cancer genome, is then delivered to the patient. Adjustments can then be made after reanalysis of liquid biopsy signals.

      2.20.5 Challenges and Solutions for Precision Medicine and Veterinary Oncology

      Challenges to the field of precision medicine, and more generally to molecularly targeted therapy, must be addressed before this important and novel approach to cancer therapy will improve outcomes. These challenges include, but are not limited to, the following.