DNA sequence information can be used to develop new therapies, new diagnostic tests, and new prognostic tests. The knowledge gained from sequencing a dog's tumor can be used as the rationale for using existing therapies on a new disease, or using therapies in a more targeted and strategic manner. Treating people with cancer based not only on the histologic diagnosis but also upon the genomic information gleaned from the DNA sequencing of the cancer has dramatically improved the effectiveness of cancer therapy for many types of cancer. It is likely that this will also be true for dogs.
NGS can be used for whole exome sequencing (WES) to identify all the protein-coding regions (exons) in the genome, whole genome sequencing (WGS) to identify the coding and non-coding regions.
NGS can also be used to focally sequence portions of the genome, this is called target or panel sequencing. While WES and WGS can reveal an enormous amount of genetic information, a significant portion of this information will be of unknown clinical importance and these technologies come with a higher cost at the present time .
Target sequencing or panel sequencing often evaluates a much smaller section of the entire genome but costs are lower than WGS and WES. Typically, these panels evaluate from a few to several hundred genes or sections of genes. When used in the setting of cancer, these panels are looking for mutations or abnormalities associated with genes that have impact on oncogenicity, cell cycle proliferation, apoptosis, DNA repair, chemotherapy and radiation therapy responsiveness, angiogenesis, and the various biochemical cellular pathways associated with cancer.
FidoCure® currently utilizes a panel-based NGS.
This panel is frequently updated as relevant mutations are characterized in either canine and/or human cancers. This method allows us to interrogate the canine tumor genome more rapidly and cost-effectively than WES or WGS.
SNVs, SNPs and INDELS are some common genome variants identified by sequencing patient samples.
SNVs (single nucleotide variants) are the most common variant, and this describes one nucleotide substituted for another at a single position. These can occur at different frequencies in a specific population being sequenced. SNVs that occur with greater than 1% frequency in the general population are termed SNPs (single nucleotide polymorphisms).
SNPs help researchers identify regions important to disease development but also may be associated with non-pathogenic traits unique to an individual.
Finally INDELs represent small insertions and deletions of one or more bases in the genome. In humans, there are approximately 192-280 INDELs in each person.
During the last 20 years, since publication of the human genome, over 150 small molecules have become available to treat cancer in people.
These therapies bind to specific targets in the cell related to cancer development and resistance, hence they are called targeted therapies. This mechanism of action is quite different from traditional chemotherapy, which acts by killing all rapidly dividing cells.
Another potential benefit of incorporating targeted therapies into the veterinary oncology toolbox is due to the highly inbred genetic profile of dogs. Because of this fact, specific genetic mutations or abnormalities found in the cancers of dogs are likely found in a much higher percentage of dogs than the corresponding mutation in people, which are a much more out-bred species.
Targeted therapies may therefore be quite useful in veterinary oncology.