Modulation of cell death in the tumor microenvironment*
Section snippets
The concept of hypoxia tolerance
Evidence implicating hypoxia in the pathogenesis of solid human tumors continues to accumulate. Tumor hypoxia was hypothesized approximately 50 years ago to be important in the radiotherapeutic management of cancer because hypoxic cells are intrinsically more resistant to radiation than aerobic cells.1 This initial interest in the radiobiological consequences of tumor hypoxia formed the basis of decades of research that, in recent years, has led to a close examination of the biological
Mechanisms of hypoxia tolerance
The formation and continued proliferation of solid tumors requires persistent angiogenesis. Reminiscent of many biological processes, angiogenesis is the result of subtle and often complex interactions balancing pro- and antiangiogenic molecules. This equilibrium is upset in various diseases, including cancer. Angiogenesis is virtually nonexistent in healthy adult tissue with the exception of a few physiological processes such as wound healing and the female menstrual cycle.21, 22 Stable
Therapy implications
The fact that hypoxia negatively impacts on therapy is well established. Hypoxic cells are radiation and chemoresistant for a variety of reasons,51 and thus effective therapy requires strategies to overcome this resistance. Many attempts have been made, most of these focused on trying to restore normal oxygenation (or mimic it) to the tumor. The concept that tumor cells become hypoxic tolerant, and furthermore that the presence of microregions of hypoxia may be advantageous to overall tumor
References (120)
- et al.
Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck
Int J Radiat Oncol Biol Phys
(1997) - et al.
Changes in the oxygenation of head and neck tumors during carbogen breathing
Radiother Oncol
(1993) - et al.
Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck
Radiother Oncol
(1996) - et al.
Mutagenesis induced by the tumor microenvironment
Mutat Res
(1998) - et al.
Biological consequences of tumor hypoxia
Semin Oncol
(2001) - et al.
A matter of life and death
Cancer Cell
(2002) - et al.
Tissue gradients of energy metabolites mirror oxygen tension gradients in a rat mammary carcinoma model
Int J Radiat Oncol Biol Phys
(2001) - et al.
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1
J Biol Chem
(1994) - et al.
Oncogenic alterations of metabolism
Trends Biochem Sci
(1999) - et al.
Cellular growth and metabolic adaptations to nutrient stress environments in tumor microregions
Int J Radiat Oncol Biol Phys
(1986)
Cellular growth and metabolic adaptations to nutrient stress environments in tumor microregions
Int J Radiat Oncol Biol Phys
Adenine nucleotides and inhibition of protein synthesis in isolated hepatocytes incubated under different pO2 levels
Arch Biochem Biophys
Hypoxia as a target for combined modality treatments
Eur J Cancer
Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers
Semin Radiat Oncol
Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: Results of a retrospective study of 386 patients
Int J Radiat Oncol Biol Phys
Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: A secondary analysis of RTOG 85-27
Int J Radiat Oncol Biol Phys
The prognostic value of hemoglobin and a decrease in hemoglobin during radiotherapy in laryngeal carcinoma
Radiother Oncol
T1/T2 glottic cancer managed by external beam radiotherapy: The influence of pretreatment hemoglobin on local control
Int J Radiat Oncol Biol Phys
Radiation myelitis and survival in the radiotherapy of lung cancer
Int J Radiat Oncol Biol Phys
The effect of arterial oxygen content on the results of radiation therapy for epidermoid bronchogenic carcinoma
Int J Radiat Oncol Biol Phys
Local control of muscle-invasive bladder cancer: Preoperative radiotherapy and cystectomy versus cystectomy alone
Int J Radiat Oncol Biol Phys
Blood tests and prognosis in bladder carcinomas treated with definitive radiotherapy
Radiother Oncol
The influence of initial hemoglobin and blood pressure levels on results of radiation therapy for carcinoma of the prostate
Int J Radiat Oncol Biol Phys
Extrapolations from laboratory and preclinical studies for the use of carbogen and nicotinamide in radiotherapy
Radiother Oncol
Radiosensitization with normobaric oxygen and carbogen
Radiother Oncol
Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer
Radiother Oncol
ARCON: Experience in 215 patients with advanced head-and-neck cancer
Int J Radiat Oncol Biol Phys
Tirapazamine: a new drug producing tumor specific enhancement of platinum-based chemotherapy in non-small-cell lung cancer
Ann Oncol
Colonisation of Clostridium in the body is restricted to hypoxic and necrotic areas of tumors
Anaerobe
Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption
Neoplasia
Endostatin: An endogenous inhibitor of angiogenesis and tumor growth
Cell
Concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy
Br J Radiol
Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells
Proc Natl Acad Sci U S A
Relationship of hypoxia to metastatic ability in rodent tumours
Br J Cancer
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Nature
Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions
Cancer Res
Hypoxia-induced metastasis of human melanoma cells: Involvement of vascular endothelial growth factor-mediated angiogenesis
Br J Cancer
Response of tumour cells to hypoxia: Role of p53 and NFkB
Mol Pathol
Hypoxia, clonal selection, and the role of HIF-1 in tumor progression
Crit Rev Biochem Mol Biol
Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix
Cancer Res
Hypoxia in human soft tissue sarcomas: Adverse impact on survival and no association with p53 mutations
Br J Cancer
Regulation of hypoxia-induced angiogenesis: A chaperone escorts VEGF to the dance
J Clin Invest
Oxygenation of head and neck tumors
Cancer
Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma
Cancer Res
In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy
Nat Med
Microenvironment-induced cancer metastasis
Int J Radiat Biol
Vascular endothelial growth factor is essential for corpus luteum angiogenesis
Nat Med
Endothelial proliferation in tumours and normal tissues: continuous labelling studies
Br J Cancer
Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1
Annu Rev Cell Dev Biol
Candidate genes for the hypoxic tumor phenotype
Cancer Res
Cited by (57)
The microbiome in anti-cancer therapy
2017, Seminars in ImmunologyCitation Excerpt :The irregularity of vasculature leads to an insufficient blood supply to tumor cells [42] and ineffective chemotherapy drug delivery and response in these regions [43]. Insufficient blood supply combined with an increased oxygen demand from rapidly proliferating tumor cells, forms pockets of necrosis and hypoxia within the tumor niche [44]. These conditions, together with tumor microenvironment immune suppression, may favor local bacterial replication [45].
US-Guided optical tomography: Correlation with clinicopathologic variables in breast cancer
2013, Ultrasound in Medicine and BiologyCitation Excerpt :Fourth, we did not classify THC into oxy- and deoxy-forms. Tumor hypoxia correlates with poor prognosis attributable to tumor propagation, malignant progression and resistance to chemotherapy and radiation therapy (Hockel and Vaupel 2001a, 2001b; Wouters et al. 2003). An increase in tumor concentration of deoxyhemoglobin might, therefore, be related to hypermetabolism and poor prognosis (Nioka and Chance 2005).
Plasminogen structural domains exhibit different functions when associated with cell surface GRP78 or the voltage-dependent anion channel
2007, Journal of Biological ChemistryCitation Excerpt :Tumor hypoxia is an innate environmental factor encountered during the development of many types of human tumors, including malignant prostate tumors (48). Strong evidence suggests hypoxia is a condition necessary for the tumor progression, angiogenesis, metastasis, and therapy resistance (49). Several reports demonstrate that enhanced expression of VDAC under hypoxia may affect Ca2+ homeostasis of the vascular cell (50).
Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc
2024, Cell and BioscienceApplication of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer
2023, World Journal of Gastroenterology
- *
Address reprint requests to Bradly G. Wouters, PhD, Department of Experimental Radiation Oncology, UNS 50/Box 23, azM/University of Maastricht, Postbox 616, 6200 MD Maastricht, The Netherlands.