Hypoxia-Induced Resistance to Chemotherapy in Cancer

  • Lori M. Minassian
  • Tiziana Cotechini
  • Erin Huitema
  • Charles H. GrahamEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1136)


A major barrier to the successful management of cancer is the development of resistance to therapy. Chemotherapy resistance can either be an intrinsic property of malignant cells developed prior to therapy, or acquired following exposure to anti-cancer drugs. Given the impact of drug resistance to the overall poor survival of cancer patients, there is an urgent need to better understand the molecular pathways regulating this malignant phenotype. In this chapter we describe some of the molecular pathways that contribute to drug resistance in cancer, the role of a microenvironment deficient in oxygen (hypoxia) in malignant progression, and how hypoxia can be a significant factor in the development of drug resistance. We conclude by proposing potential therapeutic approaches that take advantage of a hypoxic microenvironment to chemosensitize therapy-resistant tumours.


Hypoxia Drug resistance Chemotherapy Tumor microenvironment HIF-1 Metastasis Autophagy Nitric oxide Glyceryl trinitrate PD-1/PD-L1 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Lori M. Minassian
    • 1
  • Tiziana Cotechini
    • 1
  • Erin Huitema
    • 1
  • Charles H. Graham
    • 1
    Email author
  1. 1.Department of Biomedical and Molecular SciencesQueen’s UniversityKingstonCanada

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