Targeting Hypoxia to Improve Non-Small Cell Lung Cancer Outcome

Ahmed Salem*, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M. L. West, James P. B. O'Connor, Corinne Faivre-Finn

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

121 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)14-30
Number of pages17
JournalJournal of the National Cancer Institute
Volume110
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • POSITRON-EMISSION-TOMOGRAPHY
  • RANDOMIZED PHASE-II
  • CONTEXTUAL SYNTHETIC LETHALITY
  • FSAIIC MURINE FIBROSARCOMA
  • RADIATION ONCOLOGY GROUP
  • EPIDERMAL-GROWTH-FACTOR
  • CARBONIC-ANHYDRASE IX
  • CONTRAST-ENHANCED-MRI
  • EVERY 3 WEEKS
  • TUMOR HYPOXIA
  • NECK-CANCER
  • RADIATION-THERAPY
  • ACTIVATED PRODRUG
  • OXYGEN-ENHANCED MRI
  • PROGNOSTIC-SIGNIFICANCE

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