Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment

Kaitlin Graham, Evan C Unger

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly proliferating cancer cells. The levels of oxygenation within the same tumor are highly variable from one area to another and can change over time. Tumor hypoxia is an important impediment to effective cancer therapy. In radiotherapy, the primary mechanism is the creation of reactive oxygen species; hypoxic tumors are therefore radiation resistant. A number of chemotherapeutic drugs have been shown to be less effective when exposed to a hypoxic environment which can lead to further disease progression. Hypoxia is also a potent barrier to effective immunotherapy in cancer treatment. Because of the recognition of hypoxia as an important barrier to cancer treatment, a variety of approaches have been undertaken to overcome or reverse tumor hypoxia. Such approaches have included breathing hyperbaric oxygen, artificial hemoglobins, allosteric hemoglobin modifiers, hypoxia activated prodrugs and fluorocarbons (FCs). These approaches have largely failed due to limited efficacy and/or adverse side effects. Oxygen therapeutics, based on liquid FCs, can potentially increase the oxygen-carrying capacity of the blood to reverse tumor hypoxia. Currently, at least two drugs are in clinical trials to reverse tumor hypoxia; one of these is designed to improve permeability of oxygen into the tumor tissue and the other is based upon a low boiling point FC that transports higher amounts of oxygen per gram than previously tested FCs.

Original languageEnglish (US)
Pages (from-to)6049-6058
Number of pages10
JournalInternational Journal of Nanomedicine
Volume13
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Oncology
Chemotherapy
Radiotherapy
Immunotherapy
Tumors
Fluorocarbons
Drug Therapy
Oxygen
Neoplasms
Hemoglobin
Therapeutics
Blood Substitutes
Oxygenation
Tumor Hypoxia
Boiling point
Conservation of Natural Resources
Prodrugs
Pharmaceutical Preparations
Disease Progression
Permeability

Keywords

  • dodecafluoropentane emulsion
  • fluorocarbon
  • oxygen therapeutics
  • solid tumor

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment. / Graham, Kaitlin; Unger, Evan C.

In: International Journal of Nanomedicine, Vol. 13, 01.01.2018, p. 6049-6058.

Research output: Contribution to journalReview article

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