title: Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents.
abstract: Rational drug discovery and development requires biomarkers to inform on target modulation and treatment efficacy. Many aspects of metabolism are altered in cancer, compared to normal tissues, and are often regulated by oncogene activation. Non-invasive imaging of spatio-temporal effects of molecularly targeted anticancer agents on tumor metabolism has considerable potential in the development and use of personalized molecular medicine approaches to cancer treatment. Here we describe how non-invasive monitoring of metabolism, using primarily magnetic resonance spectroscopy (MRS), can be used to follow treatment with novel molecularly targeted anticancer agents. We discuss how the regulation of metabolic pathways by oncogenic signaling can affect MRS-detectable metabolic signals together with the physiological factors that can influence the measured changes. Finally, the translation of these metabolic measurements from pre-clinical models to patients will be discussed.
authors.affiliation: Cancer Research UK and EPSRC Centre for Cancer Imaging, Section of Magnetic Resonance, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK. mouniab@icr.ac.uk
authors.forename: Mounia
authors.initials: M
authors.lastname: Beloueche-Babari
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D015415:Biomarkers; D002794:Choline / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D053858:Metabolic Networks and Pathways; D057054:Molecular Imaging / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D049268:Positron-Emission Tomography; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D005947:Glucose; D002794:Choline