Targeting Hypoxia to Improve Non-Small Cell Lung Cancer Outcome

J Natl Cancer Inst. 2018 Jan 1;110(1). doi: 10.1093/jnci/djx160.

Abstract

Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials. Radiotherapy dose painting strategies based on hypoxia imaging require careful refinement prior to clinical investigation. This review will summarize the role of hypoxia, highlight the potential of hypoxia as a therapeutic target, and outline past and ongoing hypoxia-targeted therapy trials in NSCLC. Evidence supporting radiotherapy dose painting based on hypoxia imaging will be critically appraised. Carefully selected hypoxia biomarkers suitable for integration within future NSCLC hypoxia-targeted therapy trials will be examined. Research gaps will be identified to guide future investigation. Although this review will focus on NSCLC hypoxia, more general discussions (eg, obstacles of hypoxia biomarker research and developing a framework for future hypoxia trials) are applicable to other tumor sites.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Clinical Trials as Topic
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Magnetic Resonance Imaging
  • Positron-Emission Tomography*
  • Radiation-Sensitizing Agents / pharmacology*
  • Radiosurgery
  • Tumor Hypoxia / drug effects*
  • Tumor Hypoxia / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Radiation-Sensitizing Agents