Promise and progress for functional and molecular imaging of response to targeted therapies.
Biomarkers to predict or monitor therapy response are becoming essential components of drug developer's armamentaria. Molecular and functional imaging has particular promise as a biomarker for anticancer therapies because it is non-invasive, can be used longitudinally and provides information on the whole patient or tumor. Despite this promise, molecular or functional imaging endpoints are not routinely incorporated into clinical trial design. As the costs of clinical trials and drug development become prohibitively more expensive, the need for improved biomarkers has become imperative and thus, the relatively high cost of imaging is justified. Imaging endpoints, such as Diffusion-Weighted MRI, DCE-MRI and FDG-PET have the potential to make drug development more efficient at all phases, from discovery screening with in vivo pharmacodynamics in animal models through the phase III enrichment of the patient population for potential responders. This review focuses on the progress of imaging responses to new classes of anti-cancer therapies targeted against PI3 kinase/AKT, HIF-1alpha and VEGF. The ultimate promise of molecular and functional imaging is to theragnostically predict response prior to commencement of targeted therapy.
Stephen
Renu M
RM
Arizona Cancer Center, University of Arizona, 1515 N. Campbell, P.O. box: 245024, Tucson, Arizona 85724, USA. rms3@email.arizona.edu
Gillies
Robert J
RJ
D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D009369:Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D049268:Positron-Emission Tomography; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D015415:Biomarkers; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose