Pre-clinical development of hypoxia-based strategies for cancer treatment.
Lead Research Organisation:
University of Manchester
Department Name: Manchester Pharmacy School
Abstract
Hypoxic cells in tumours comprise a sub-population of cells that are resistant to radio-and chemotherapy. The greater the proportion of hypoxic cells in tumours the greater chance of resistance to therapy in the clinic and the bigger chance of the development of metastatic disease. The Stratford/Williams group are working towards understanding the mechanistic basis of these hypoxia-mediated processes. In achieving this they are identifying new molecular targets which can be used for drug therapy.
To achieve these objectives this group combines the expertise of medicinal chemistry and pharmacology with molecular, cell and tumour biology
To achieve these objectives this group combines the expertise of medicinal chemistry and pharmacology with molecular, cell and tumour biology
Technical Summary
The presence of hypoxic cells in tumours is a major barrier to cancer treatment. However, tumour hypoxia constitutes a unique physiological abnormality which can be exploited to develop more effective treatments. This research proposal seeks to develop novel hypoxia-mediated therapeutic approaches and the objectives of our research are:
* Gain an understanding of the underlying mechanisms by which Hypoxia Inducible Factor-1 (HIF-1) can influence tumour growth and response to radiation or chemotherapy. Then use this information to develop small molecule inhibitors of HIF.
* To determine whether downstream targets of HIF activity, such as Carbonic anhydrase IX (CAIX), VEGF or nitric oxide synthase (NOS) can be exploited for therapeutic benefit.
* Develop a platform technology for hypoxia-mediated bioreductive drug activation and delivery.
* Determine the roles of hypoxia and HIF in metastatic disease, and define the therapeutic role of bioreductive drugs in the treatment of metastases.
* To provide further information to validate the concept of hypoxia-mediated gene therapy for the treatment of solid tumours.
The overall goal of this translational research is to facilitate the introduction of new entities/modalities into cancer treatment.
* Gain an understanding of the underlying mechanisms by which Hypoxia Inducible Factor-1 (HIF-1) can influence tumour growth and response to radiation or chemotherapy. Then use this information to develop small molecule inhibitors of HIF.
* To determine whether downstream targets of HIF activity, such as Carbonic anhydrase IX (CAIX), VEGF or nitric oxide synthase (NOS) can be exploited for therapeutic benefit.
* Develop a platform technology for hypoxia-mediated bioreductive drug activation and delivery.
* Determine the roles of hypoxia and HIF in metastatic disease, and define the therapeutic role of bioreductive drugs in the treatment of metastases.
* To provide further information to validate the concept of hypoxia-mediated gene therapy for the treatment of solid tumours.
The overall goal of this translational research is to facilitate the introduction of new entities/modalities into cancer treatment.