Unlike adjacent normal tissues, low oxygen and glucose levels characterize the prostate cancer’s environment. The AMP-activated protein kinase (AMPK) pathway is expressed in the human prostate and it is activated in response to these stressful conditions. Activation of this pathway leads to a therapy-resistant state that will be investigated.
These studies will advance our knowledge of the mechanisms by which the prostate environment modifies tumor radiosensitivity and support a role for the AMPK pathway in the therapy resistance of clinically localized prostate cancer. Our study would help in establishing a novel target for therapeutic radiosensitization of stressed tumors such as prostate cancer. These studies are particularly relevant, because drugs such as metformin and rosiglitazone, known activators of the AMPK signal transduction pathway, are used by thousands of Americans for the management of type II diabetes mellitus and could be adversely effecting cancer therapy.