Fluorescent Sensors of Protein Kinases: From Basics to Biomedical Applications - Progress in Molecular Biology and Translational Science - page 259

Fundamental studies

￿ Gene expression

￿ Protein kinase activity—activation & kinetics

￿ Spatiotemporal localization

￿ Molecular and conformational dynamics

Biomedical applications

Drug discovery programmes

￿ Clinical diagnostics for early detection

￿ HTS / HCS screening

￿ Monitoring disease progression through target

dysregulation

￿ Postscreening characterization of hits

￿ ￿ Assessing therapeutic benefits following

administration of drugs

Optimization of leads

￿ Preclinical imaging and evaluation of

drug candidates ￿ Monitoring resistance emergence

￿ Image-guided surgery

Figure 6.15 Applications of fluorescent kinase biosensors. Fluorescent biosensors can be
applied to probe the function, regulation, and spatiotemporal dynamics of protein
kinases in fundamental studies. Aside from their utility in fundamental research, they
constitute potent tools for biomedical and drug discovery approaches. Biomedical
applications include development of clinical diagnostics, through imaging disease bio-
markers, monitoring disease progression, and response to therapeutics. Drug discovery
approaches include high-throughput screening and postscreening evaluation of lead
compounds and drug candidates.

4.2. Monitoring protein kinase biomarkers in clinical
diagnostics
From a biomedical perspective, fluorescent biosensors constitute very attrac-
tive tools for probing differential or aberrant activation of protein kinases in a
pathological context and have a number of practical applications in several
areas of health and disease, including clinical diagnostics and monitoring re-
sponse to therapeutics. For instance, imaging protein kinases that constitute
disease biomarkers, thanks to biosensors whose fluorescence is affected by
their activity, can provide a wealth of information on the functional status
of these enzymes. In this respect, fluorescent biosensors provide a basis for
the development of diagnostic strategies involving detection of protein
kinase biomarkers whose activity is dysregulated in pathological disorders
or involved in disease pathogenesis . Although there are still very few fluo-
rescent biosensors that have actually been applied to detect protein kinases in
a diagnostic perspective, a couple of noteworthy examples are currently
employed for clinical diagnostics of dysregulated protein kinases in cancer.
The genetically encoded FRET biosensor developed by Mizutani et al.
for detection of Bcr-Abl kinase activity allows the detection of cancerous