Dogs have been studied for many years as a medical diagnostic tool to detect a
pre-clinical disease state by sniffing emissions directly from a human or an in
vitro biological sample. Some of the studies report high sensitivity and
specificity in blinded case-control studies. However, in these studies it is completely
unknown as to which suites of chemicals the dogs detect and how they ultimately interpret
this information amidst confounding background odors. Herein, we consider the advantages
and challenges of canine olfaction for early (meaningful) detection of cancer, and propose
an experimental concept to narrow the molecular signals used by the dog for sample
classification to laboratory-based instrumental analysis. This serves two purposes; first,
in contrast to dogs, analytical methods could be quickly up-scaled for high throughput
sampling. Second, the knowledge gained from identifying probative chemicals could be
helpful in learning more about biochemical pathways and disease progression. We focus on
exhaled breath aerosol, arguing that the semi-volatile fraction should be given more
attention. Ultimately, we conclude that the interaction between dog-based and
instrument-based research will be mutually beneficial and accelerate progress towards
early detection of cancer by breath analysis.