Hypoxia activated prodrugs
Encyclopedia
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. It is believed that tumor hypoxia contributes significantly to treatment failure and relapse among cancer patients because cells in the hypoxic zones of solid tumors resist traditional chemotherapy for at least two reasons: first, most antitumor agents cannot penetrate beyond 50-100 micrometers from capillaries, thereby never reaching those cells in the hypoxic regions. Secondly, the lower nutrient and oxygen supply to cells in the hypoxic zones of tumors cause them to divide more slowly than their well oxygenated counterparts, so hypoxic tumor cells exhibit greater resistance to chemotherapies and radiation which target rapidly dividing cells or require oxygen for efficacy.
Hypoxia also contributes to the invasive and metastatic phenotypes of aggressive cancers by promoting genetic instability and accelerating the accumulation of mutations that can ultimately give rise to drug resistance.
There are several companies developing HAPs: 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).
Tumor hypoxia
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...
within tumor cells. HAPs may offer the potential, alone and in combination with conventional chemotherapy, of improving cancer therapy. It is believed that tumor hypoxia contributes significantly to treatment failure and relapse among cancer patients because cells in the hypoxic zones of solid tumors resist traditional chemotherapy for at least two reasons: first, most antitumor agents cannot penetrate beyond 50-100 micrometers from capillaries, thereby never reaching those cells in the hypoxic regions. Secondly, the lower nutrient and oxygen supply to cells in the hypoxic zones of tumors cause them to divide more slowly than their well oxygenated counterparts, so hypoxic tumor cells exhibit greater resistance to chemotherapies and radiation which target rapidly dividing cells or require oxygen for efficacy.
Hypoxia also contributes to the invasive and metastatic phenotypes of aggressive cancers by promoting genetic instability and accelerating the accumulation of mutations that can ultimately give rise to drug resistance.
There are several companies developing HAPs: 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).