Radiolabelled receptor-tyrosine-kinase targeting drugs for patient stratification and monitoring of therapy response: prospects and pitfalls

Lancet Oncol. 2010 Oct;11(10):992-1000. doi: 10.1016/S1470-2045(10)70088-7. Epub 2010 Jul 26.

Abstract

Transmembrane receptor tyrosine kinases (RTKs) are overexpressed in many malignancies. RTK signalling triggers cell proliferation, suppression of apoptosis, increased motility, and recruitment of neovasculature. Overexpressed RTKs are the molecular targets for an increasing number of anticancer drugs. Monoclonal antibodies block the ligands or their binding sites and prevent receptor dimerisation, thereby hindering RTK signalling. The antibody-dependent cellular cytotoxicity can boost the therapeutic effect. Small-molecule tyrosine kinase inhibitors (TKIs) hamper downstream RTK signalling by targeting the intracellular kinase domain. These drugs have significantly increased survival in several patient groups. Improved patient stratification and therapy monitoring might further enhance the efficacy of anti-RTK therapy. Radionuclide-based molecular imaging can provide methods for localising and estimating the expression of RTKs. It can potentially identify patients who have tumours that overexpress RTK and would, therefore, most likely benefit from a targeted treatment. Monitoring changes in RTK expression during therapy could help avoid overtreatment and undertreatment. Radionuclide-based methods are less invasive and less sensitive to expression heterogeneity than more conventional sampling methods. The biochemical information is also obtained in an anatomical context. The development of radiolabelled anti-RTK drugs and their analogues is the subject of intensive preclinical and translational research. In this review, we present current approaches to developing imaging probes for in-vivo RTK visualisation and discuss their advantages and disadvantages.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Drug Monitoring*
  • Humans
  • Ligands
  • Molecular Imaging*
  • Neoplasms / diagnosis*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Patient Selection*
  • Precision Medicine
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / therapeutic use
  • Radiopharmaceuticals*
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Ligands
  • Protein Kinase Inhibitors
  • Radiopharmaceuticals
  • Receptor Protein-Tyrosine Kinases