Men with advanced prostate cancer can experience tumor progression despite maximum blockade of their androgen pathway
Prostate cancer is the second most common cancer in men worldwide.1 More than 164,000 men in the United States are estimated to be newly diagnosed with prostate cancer in 2018.2 Castration-resistant prostate cancer (CRPC) refers to the subset of men whose prostate cancer progresses despite castrate levels of testosterone (less than 50 ng/dL).3
Prostate cancer that is localized to the prostate can be effectively treated with surgery, radiation, brachytherapy and other modalities in an effort to eradicate all disease and cure the patient. In some cases, the tumor advances locally or metastasizes (grows in places outside of the prostate); these are examples of advanced prostate cancer. The goal of treatment for advanced prostate cancer is to control the tumor and keep the patient alive and well for as long as possible.
In advanced prostate cancer, a number of treatments with hormone blocking therapies or chemotherapy are used to slow the spread of metastases, shrink existing tumors, reduce symptoms and improve quality of life. Although most men with advanced prostate cancer are not cured of their disease, they can live a normal life for many years.
Hormone therapy, also referred to as androgen deprivation therapy (ADT), is typically the first line of treatment for advanced prostate cancer. Male hormones called androgens (which include testosterone) can enhance the growth of prostate cancer cells. Reducing or blocking these hormones can deprive cancer cells of the fuel they need to grow. Many men are effectively treated with male anti-androgen therapy.
Many men with advanced prostate cancer have alterations or different forms of their androgen receptor within their prostate cancer which may make them not as responsive to ADT or develop resistance to these therapies. Specific genetic variants causing changes in protein structure (splice variants) or leading to mutations can occur in tumors (for example, the mutation AR-V7). Further, the body may respond to ADT with the increased production of local androgens that can drive cancer growth. These patients will have tumor progression despite maximum blockade of their androgen pathway and are described as having Castrate-Resistant Prostate Cancer (CRPC). In the absence of other hormonal approaches, these patients may be prescribed chemotherapy drugs or other therapeutic approaches.
Selective Androgen Receptor Degraders (SARDs) are a new class of drugs being pioneered by GTx. The principal goal of SARDs is to not only bind to the androgen receptors, but also to degrade those receptors, resulting in the increased ability to circumvent common drug resistance in prostate cancer patients. The Company believes that SARD compounds should be able to degrade multiple forms of the androgen receptor (AR), including AR variants, such as AR-V7 as well as mutants that lead to resistance.
1 American Cancer Society. Global Cancer Facts and Figures (2015).
2 American Cancer Society. Key Statistics for Prostate Cancer.
3 Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011;65(11):1180-92.