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

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.

Oxygen-dependent regulation of tumor growth and metastasis in human breast cancer xenografts.

Tumor hypoxia is relevant for tumor growth, metabolism, resistance to chemotherapy and metastasis. We have previously shown that hyperoxia, using hyperbaric oxygen treatment (HBOT), attenuates tumor growth and shifts the phenotype from mesenchymal to epithelial (MET) in the DMBA-induced mammary tumor model. This study describes the effect of HBOT on tumor growth, angiogenesis, chemotherapy efficacy and metastasis in a triple negative MDA-MB-231 breast cancer model, and evaluates tumor growth using a triple positive BT-474 breast cancer model. 5 x 105 cancer cells were injected s.c. in the groin area of NOD/SCID female mice. The BT-474 group was supplied with Progesterone and Estradiol pellets 2-days prior to tumor cell injection. Mice were divided into controls (1 bar, pO2 = 0.2 bar) or HBOT (2.5 bar, pO2 = 2.5 bar, 90 min, every third day until termination of the experiments).

Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours.

Hyperbaric oxygen (HBO) therapy is widely used as an adjunctive treatment for various pathological states, predominantly related to hypoxic and/or ischaemic conditions. It also holds promise as an approach to overcoming the problem of oxygen deficiency in the poorly oxygenated regions of the neoplastic tissue. Occurrence of local hypoxia within the central areas of solid tumours is one of the major issues contributing to ineffective medical treatment. However, in anti-cancer therapy, HBO alone gives a limited curative effect and is typically not applied by itself. More often, HBO is used as an adjuvant treatment along with other therapeutic modalities, such as radio- and chemotherapy.

Hyperbaric oxygen therapy and cancer–a review.

Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing O(2) delivery to the tissue. Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence.

Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies.

Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO(2)) may be an effective option for some patients. In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded.

The effect of oxygenation on the biological behaviour of tumours.

Malignant tumours often display hypoxic tissue areas where the oxygen tension is < 7 mm Hg. Studies in this field have proved that the hypoxic state boosts tumour progression and aggressive behaviour. In tissue culture experiments "in vitro" oxygenation was found to inhibit in itself the proliferation of cells of healthy tissues as well as benign and malignant tumours. It is a very important observation from oncotherapeutic point of view that in the presence of partial oxygen pressure < 2.5 mm Hg the radiosensitivity decreases (intrinsic radioresistance). Most of the anticancer drugs (cytostatics) are also ineffective in hypoxic tumours (chemoresistance).

Key Cancer Research