Tumor hypoxia
Encyclopedia
Tumor hypoxia is the situation where tumor
cells
have been deprived of oxygen
. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic tumor cells are usually resistant to radiotherapy and chemotherapy
, but they can be made more susceptible to treatment by increasing the amount of oxygen in them. Bioreductive prodrugs also play a significant part in dealing with these kinds of cells: they can kill the oxygen-deficient tumor cells selectively as hypoxic cytotoxins. The study of tumors in such conditions was pioneered by Dr L. H. Gray
.
Tumor hypoxia can also be a result of the high degree of cell proliferation undergone in tumor tissue which causes a higher cell density and thus taxes the local oxygen supply.
There are several companies working to address tumor hypoxia: Novacea, Inc., Proacta Inc. and Threshold Pharmaceuticals, Inc. These companies are developing the following drug candidates: AQ4N (Novacea), PR-104 (Proacta) and TH-302
(Threshold Pharmaceuticals). These drug candidates target levels of hypoxia that are common in tumors but are rare in normal tissues. The hypoxic zones of tumors generally evade traditional chemotherapeutic agents and ultimately contribute to relapse. In the literature, hypoxia has been demonstrated to be associated with a worse prognosis, making it a determinant of cancer progression and therapeutic response. Several recent review articles summarize the current status of hypoxic cytotoxins (hypoxia activated prodrugs
).
Niacinamide, the active form of vitamin B3, acts as a chemo- and radio-sensitizing agent by enhancing tumor blood flow, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.http://www.cancer.gov/drugdictionary/?CdrID=42044.
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
have been deprived of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic tumor cells are usually resistant to radiotherapy and chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, but they can be made more susceptible to treatment by increasing the amount of oxygen in them. Bioreductive prodrugs also play a significant part in dealing with these kinds of cells: they can kill the oxygen-deficient tumor cells selectively as hypoxic cytotoxins. The study of tumors in such conditions was pioneered by Dr L. H. Gray
Louis Harold Gray
Louis Harold Gray was a British physicist who worked mainly on the effects of radiation on biological systems, inventing the field of radiobiology as he went. A summary of his work is given below...
.
Tumor hypoxia can also be a result of the high degree of cell proliferation undergone in tumor tissue which causes a higher cell density and thus taxes the local oxygen supply.
There are several companies working to address tumor hypoxia: Novacea, Inc., Proacta Inc. and Threshold Pharmaceuticals, Inc. These companies are developing the following drug candidates: AQ4N (Novacea), PR-104 (Proacta) and TH-302
TH-302
TH-302 is an experimental cancer treatment that is in clinical development at Threshold Pharmaceuticals, Inc. It is activated only at very low levels of oxygen . Such levels are common in human solid tumors, a phenomenon known as tumor hypoxia...
(Threshold Pharmaceuticals). These drug candidates target levels of hypoxia that are common in tumors but are rare in normal tissues. The hypoxic zones of tumors generally evade traditional chemotherapeutic agents and ultimately contribute to relapse. In the literature, hypoxia has been demonstrated to be associated with a worse prognosis, making it a determinant of cancer progression and therapeutic response. Several recent review articles summarize the current status of hypoxic cytotoxins (hypoxia activated prodrugs
Hypoxia activated prodrugs
Hypoxia Activated Prodrugs, or HAPs, target regions of tumor hypoxia within tumor cells. HAPs may offer the potential, alone and in combination with conventional chemotherapy, of improving cancer therapy...
).
Niacinamide, the active form of vitamin B3, acts as a chemo- and radio-sensitizing agent by enhancing tumor blood flow, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.http://www.cancer.gov/drugdictionary/?CdrID=42044.