[Frontiers in Bioscience 16, 1996-2007, June 1, 2011]

Assessment of tumor response to tyrosine kinase inhibitors

Amanda Lowery, Zhaozhong Han

Department of Radiation Oncology, School of Medicine, Vanderbilt University,Nashville, TN

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. RTKs and TKI
3.1. RTK in cancer development
3.2. RTK as a therapeutic target and TKIs as targeted therapies
4. Predictive biomarkers for tumor susceptibility to TKIs
5. Ex vivo and In vitro Biological and biochemical assessment of TKI efficacy
5.1. Substrate phosphorylation and downstream signal mediator activation
5.2. Pharmacokinetics
5.3. Metabolic and blood biochemistry changes
5.3.1. Circulating endothelial cells and cancer cells
5.3.2. Growth factors and soluble growth factor receptors
6. Response to TKI by non-invasive imaging
6.1. Anatomical Imaging
6.1.1. Magnetic Resonance Imaging (MRI)
6.1.2. Computed Tomography (CT)
6.1.3. Ultrasound (US)
6.2. Functional Imaging
6.2.1. Metabolism within tumors
6.2.2. Cell proliferation
6.2.3. Hypoxia
6.2.4. Apoptosis
6.2.5. Vascularity
6.3. Molecular Imaging
6.3.1. Receptor imaging
6.3.2. Caspase 3 imaging
6.3.3. New imaging peptides and antibodies
7. Conclusions
8. Acknowledgements
9. References

1. ABSTRACT

This review briefly summarizes recent developments in the use of non-invasive imaging to assess tumor response to TKI therapy. Receptor tyrosine kinases play important roles in cancer development. A new class of drugs, tyrosine kinase inhibitors (TKI) can induce rapid and dramatic tumor suppression when administered to carefully selected patient groups. Identifying these patients with responding tumors prior to or shortly after the initiation of therapy remains challenging. The gold standard of response assessment has been by invasive biopsies used in biological and biochemical procedures. Advances in non-invasive imaging at the anatomical, functional and molecular level have enabled the early detection of tumor response; sometimes within days of beginning treatment. The growing area of molecular imaging has spurred the discovery of novel targeting peptides to bind TKI responding tumors. The emergence of targeted, quick responding imaging probes advances the field of cancer management towards the goal of personalized medicine.