Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response
Tóm tắt
After completing this course, the reader will be able to:
Explain the effect of hypoxia on resistance to treatment. Describe the causes of tumor hypoxia. Characterize cellular response to hypoxia.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O2) supply and consumption. Major causative factors of tumor hypoxia are abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O2 transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O2-dependent cytotoxic agents, and photodynamic therapy. Tumor hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate tumor hypoxia and support a vicious circle of increasing hypoxia and malignant progression while concurrently promoting the development of more treatment-resistant disease. This pattern of malignant progression, coupled with the demonstration of a relationship between falling hemoglobin level and worsening tumor oxygenation, highlights the need for effective treatment of anemia as one approach for correcting anemic hypoxia in tumors, and in so doing, possibly improving therapeutic response.
Từ khóa
Tài liệu tham khảo
Schwarz, 1909, Über Desensibilisierung gegen Röntgen- und Radiumstrahlen, Münchener Med Wochenschr, 24, 1
Mottram, 1931, A factor of importance in the radio-sensitivity of tumours, Br J Radiol, 9, 606, 10.1259/0007-1285-9-105-606
Gray, 1953, The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy, Br J Radiol, 26, 638, 10.1259/0007-1285-26-312-638
Teicher, 1990, Classification of antineoplastic treatments by their differential toxicity toward putative oxygenated and hypoxic tumor subpopulations in vivo in the FSaIIC murine fibrosarcoma, Cancer Res, 50, 3339
Littlewood, 2001, The impact of hemoglobin levels on treatment outcomes in patients with cancer, Semin Oncol, 28, 49, 10.1016/S0093-7754(01)90213-1
Höckel, 1991, Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements, Cancer Res, 51, 6098
Vaupel, 1991, Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements, Cancer Res, 51, 3316
Vaupel, 2001, Treatment resistance of solid tumors: role of hypoxia and anemia, Med Oncol, 18, 243, 10.1385/MO:18:4:243
Vaupel, 2001, Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy, Semin Oncol, 28, 29, 10.1016/S0093-7754(01)90210-6
Vaupel, 2002, Hypoxia in breast cancer: pathogenesis, characterization and biological/therapeutic implications, Wien Med Wochenschr, 152, 334, 10.1046/j.1563-258X.2002.02032.x
Höckel, 2001, Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects, J Natl Cancer Inst, 93, 266, 10.1093/jnci/93.4.266
Vaupel, 2002, Oxygenation status of gynecologic tumors: what is the optimal hemoglobin level?, Strahlenther Onkol, 178, 727, 10.1007/s00066-002-1081-x
Vaupel, 2003, Oxygenation gain factor: a novel parameter characterizing the association between hemoglobin level and the oxygenation status of breast cancers, Cancer Res, 63, 7634
Zander, 1996, [Oxygen supply and acid-base status in extreme anemia.] Anaesthesiol Intensivmed Notfallmed Schmerzther, 31, 492
Becker, 2000, Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas, Int J Radiat Oncol Biol Phys, 46, 459, 10.1016/S0360-3016(99)00384-3
Höckel, 2001, Biological consequences of tumor hypoxia, Semin Oncol, 28, 36, 10.1016/S0093-7754(01)90211-8
Moulder, 1987, Tumor hypoxia: its impact on cancer therapy, Cancer Metastasis Rev, 5, 313, 10.1007/BF00055376
Durand, 1991, Keynote address: the influence of microenvironmental factors on the activity of radiation and drugs, Int J Radiat Oncol Biol Phys, 20, 253, 10.1016/0360-3016(91)90100-I
Giaccia, 1996, Hypoxic stress proteins: survival of the fittest, Semin Radiat Oncol, 6, 46, 10.1016/S1053-4296(96)80035-X
Riva, 1998, Cellular physiology and molecular events in hypoxia-induced apoptosis, Anticancer Res, 18, 4729
Haroon, 2000, Early wound healing exhibits cytokine surge without evidence of hypoxia, Ann Surg, 231, 137, 10.1097/00000658-200001000-00020
Goda, 2003, Hypoxia-inducible factor 1 alpha is essential for cell cycle arrest during hypoxia, Mol Cell Biol, 23, 359, 10.1128/MCB.23.1.359-369.2003
Koumenis, 2001, Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation, Mol Cell Biol, 21, 1297, 10.1128/MCB.21.4.1297-1310.2001
Soengas, 1999, Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition, Science, 284, 156, 10.1126/science.284.5411.156
Prehn, 1991, The inhibition of tumor growth by tumor mass, Cancer Res, 51, 2
Demicheli, 1994, Local recurrences following mastectomy: support for the concept of tumor dormancy, J Natl Cancer Inst, 86, 45, 10.1093/jnci/86.1.45
Holmgren, 1995, Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression, Nat Med, 1, 149, 10.1038/nm0295-149
Folkman, 1995, Clinical applications of research on angiogenesis, N Engl J Med, 333, 1757, 10.1056/NEJM199512283332608