Page 176 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 8 Molecular Diagnostics 155

“I have some idea on treatments but want to prioritize the best and negative predictive values, is the need to understand carefully
therapy.” It is not uncommon that the selection of the best treat- the relevance of the patient populations used in manuscripts that
describe assay performance. Assay performance is closely regulated
ment for a cancer histology is unclear and often defaults to the
VetBooks.ir clinician’s preference (e.g., selection of a specific cytotoxic che- in the human molecular diagnostics field (e.g., Clinical Laboratory
Improvement Amendments [CLIA] laboratory certification), but
motherapy for canine bladder carcinoma). A distinct PMED
approach may provide assistance in known drug selection. The such regulation is absent in the veterinary reference laboratory diag-
theoretical value of selecting the best drug, based on intrinsic nostic model. Therefore rigor and the requirement of transparency
resistance and sensitivity signatures, may be effectively provided appropriately become the responsibility of the diagnostic scientist
through transcriptomic, proteomic, and cell-based PMED plat- and must be demanded and understood by the attending clinician.
forms. The validation of these drug selection strategies will require
prospective validation in specific cancers in which cohorts of indi- Summary
viduals may receive a PMED-described medication compared
with clinician’s best choice. Such transcriptomic, proteomic, and Molecular diagnostics is becoming more integrated into veteri-
cell-based PMED platforms are less likely to identify specific driv- nary medicine and at the same time becoming more affordable.
ers of cancer biology and generate new options for therapy. One important feature of such advanced diagnostics is that many
An ever-growing array of tests designed to inform diagnostic of these techniques save money for owners and eliminate the need
and treatment decisions in the human clinic is available from for invasive procedures for their pets. For example, sensitive meth-
more than 100 academic and 50 commercial laboratories. These ods for detecting lymphoma through a combination of cytology,
tests range in scope from single genes to gene panels, exomes, and flow cytometry, and PARR assays can mean that a diagnosis of
even whole genomes. Indeed, the multiomic analysis of cancer splenic lymphoma can be made without splenectomy. Detection
(multiple modalities used in a single cancer) is now common and of the c-kit mutation can guide therapy so that the most effica-
has reulted in a need to display and share such multiomic data. cious (and therefore cost-effective) drugs are used. More expensive
In everyday clinical practice the cost is still prohibitive, and the exploratory techniques, such as whole genome sequencing and
expertise and infrastructure required to bring them to bear on proteomic analysis of tumors, will almost certainly lead to discov-
patient care are also largely lacking. Finally, more comprehensive ery of new testing that can further simplify diagnoses. Veterinar-
data showing improvements in genomics-correlated clinical out- ians are encouraged to participate in these developmental studies
comes is needed to support the use of these tests. when they can, by providing biologic materials and clinical data
to researchers, because ultimately patients and their owners will
The Path to PMED for Veterinary Cancer Patients derive great benefit from current research.

Although much work remains to be done to chart the genomic References
landscapes of companion animal cancers, the PMED approach
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cutting edge opportunity in veterinary cancer care and is the sub- 2. London CA, Malpas PB, Wood-Follis SL, et al.: Multi-center,
ject of ongoing prospective clinical trials. In fact, not only would placebo-controlled, double-blind, randomized study of oral tocera-
this approach make great headway in the care of canine cancer nib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for
patients, but also, given the unique aspects of naturally occur- the treatment of dogs with recurrent (either local or distant) mast
ring cancer in pet dogs and the forward-thinking perspectives of cell tumor following surgical excision, Clin Cancer Res 15:3856–
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It has been historically acceptable for one laboratory to describe 7. Breen M, Modiano JF: Evolutionarily conserved cytogenetic
the performance of a specific assay in their hands and for clini- changes in hematological malignancies of dogs and humans—man
and his best friend share more than companionship, Chromosome Res
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performed by a distinct laboratory. Indeed, based on this expected 8. Thomas R, Seiser EL, Motsinger-Reif A, et al.: Refining tumor-asso-
consistency of analysis among laboratories, there was little need ciated aneuploidy through ‘genomic recoding’ of recurrent DNA
for distinct laboratories performing the same assay to publish their copy number aberrations in 150 canine non-Hodgkin lymphomas,
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to come to the field of molecular diagnostics, and clinicians should 9. Hedan B, Thomas R, Motsinger-Reif A, et al.: Molecular cytogenetic
expect the publication of a laboratory experience with a given characterization of canine histiocytic sarcoma: a spontaneous model
assay and should not expect the performance of the assay to be the for human histiocytic cancer identifies deletion of tumor suppres-
same across laboratories. Further complicating the issue of assay sor genes and highlights influence of genetic background on tumor
performance, characterized by sensitivity, specificity, and positive behavior, BMC Cancer 11:201–215, 2011.