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Hypoxia and Anemia: Factors in Decreased Sensitivity to Radiation Therapy and Chemotherapy?

Louis Harrisona, Kimberly Blackwellb

a Beth Israel Medical Center, New York, New York, USA; b Duke University Medical Center, Durham, North Carolina, USA

Correspondence: Louis Harrison, M.D., Department of Radiation Oncology, Beth Israel Medical Center, St. Lukes Roosevelt Hospital Center, 10 Union Square East, New York, New York 10003-3314, USA. Telephone: 212-844-8087; Fax: 212-844-8086; e-mail: Lharrison{at}bethisraelny.org

Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO2] value ≤10 mmHg) is associated with lower overall and disease-free survival, greater recurrence, and less locoregional control in head and neck carcinoma, cervical carcinoma, and soft-tissue sarcoma. In view of the deleterious effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.

Key Words. Hypoxia • Anemia • Radiotherapy • Hemoglobin • Chemotherapy • Outcomes • Epoetin alfa




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