Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects

Abstract

Tissue hypoxia results from an inadequate supply of oxygen (O(2)) that compromises biologic functions. Evidence from experimental and clinical studies increasingly points to a fundamental role for hypoxia in solid tumors. Hypoxia in tumors is primarily a pathophysiologic consequence of structurally and functionally disturbed microcirculation and the deterioration of diffusion conditions. Tumor hypoxia appears to be strongly associated with tumor propagation, malignant progression, and resistance to therapy, and it has thus become a central issue in tumor physiology and cancer treatment. Biochemists and clinicians (as well as physiologists) define hypoxia differently; biochemists define it as O(2)-limited electron transport, and physiologists and clinicians define it as a state of reduced O(2) availability or decreased O(2) partial pressure that restricts or even abolishes functions of organs, tissues, or cells. Because malignant tumors no longer execute functions necessary for homeostasis (such as the production of adequate amounts of adenosine triphosphate), the physiology-based definitions of the term "hypoxia" are not necessarily valid for malignant tumors. Instead, alternative definitions based on clinical, biologic, and molecular effects that are observed at O(2) partial pressures below a critical level have to be applied.

Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinoma

“…No studies measuring O 2 tension in breast carcinoma in relation to patient survival have been published; however, in patients with cervical carcinoma, it is known that in vivo intratumoral hypoxia predicts poor survival. 1 In the current study and in our previous report, 19 HIF-1␣ staining often was observed in viable cells surrounding areas of necrosis, suggesting that hypoxia contributes to HIF-1␣ up-regulation in breast carcinoma. Adaptation to hypoxia is mediated by HIF-1, which stimulates angiogenesis (through VEGF) and high and anaerobic metabolism (through glucose transporters and glycolytic enzymes).…”

Enhanced Photodynamic Cancer Treatment by Mitochondria‐Targeting and Brominated Near‐Infrared Fluorophores

“…The advantages of PDT are that it is a noninvasive treatment and the generated reactive oxygen species (ROS) have a short lifetime and diffusion range (0.1 µm); treatment at restricted sites is therefore possible 2, 3. However, PDT also has some drawbacks as a first‐line therapy because its effectiveness is reduced when the oxygen supply is lowered in tumors due to their microvessel structure and microcirculation, and because of oxygen consumption by the PDT process 4. In addition, PDT agents may cause genetic variation when they are taken up by organelles such as the nucleus 5.…”

Pretreatment serum lactate dehydrogenase is an independent prognostic factor for patients receiving neoadjuvant chemotherapy for locally advanced cervical cancer

“…For locally advanced solid tumors, hypoxia is a characteristic property due to rapid cancer cell proliferation, high metabolic demands, and functional angiogenesis 8. There is clear evidence that hypoxia can promote cancer development and it is involved in the resistance to treatment via the formation of new blood vessels 9.…”