About Resistant Prostate Cancer
Every year, more than 200,000 men are diagnosed with prostate cancer. According to the American Cancer Society, prostate cancer is the most frequently diagnosed cancer among men in the United States and is the second leading cause of cancer related death in this group.
Prostate cancer tumors are unique in that their growth is fueled by androgens, or male sex hormones, which are produced mainly in the testes. Current therapies designed to reduce androgens by medical or surgical castration can be effective initially in controlling prostate cancer, but resistance to these therapies usually occurs, rendering them ineffective after several years. Resistant prostate cancer, also known as castration resistant prostate cancer (CRPC) or hormone refractory prostate cancer (HRPC), is an advanced form of prostate cancer that does not respond to first-line prostate cancer treatment and continues to thrive after a period of successful therapy.
It is estimated that there are 60,000 new cases of resistant prostate cancer in the United States annually, and nearly all men initially diagnosed with prostate cancer will advance to this resistant form of the disease. The only therapy currently approved for the treatment of progression of resistant prostate cancer is the chemotherapeutic docetaxel. New therapies are needed to specifically address the multiple mechanisms that allow prostate cancer cells to grow. TOK-001 is the only compound in development that combines three distinct mechanisms of action for the treatment of resistant prostate cancer.
About TOK-001: Three Distinct Mechanisms of Action
TOK-001 is a small molecule, oral drug that disrupts the growth and survival of cancer cells by attacking three specific targets in the prostate cancer tumor, providing a novel and proprietary triple mechanism of action (MOA) for the treatment of CRPC.
CRPC cells become resistant to therapy by developing alternative mechanisms for satisfying their androgen requirement. CRPC cells:
- Synthesize their own androgens
- Rely on low-level androgens secreted by the adrenal glands
- Increase the number of androgen receptors they contain, becoming more androgen responsive
Androgen receptor antagonists have demonstrated clinical effectiveness in the treatment of prostate cancer, with one currently available to patients (bicalutamide) and another in Phase 3 clinical trials (MDV3100). There is also a CYP17 lyase inhibitor currently in Phase 3 clinical trials (abiraterone) and the compound has demonstrated reduction in prostate-specific antigen (PSA) levels. Notably, TOK-001 is the first investigational new drug that decreases androgen receptor levels in prostate cancer cells and the only prostate cancer compound in development in which all three of these distinct mechanisms are combined in one drug.
In preclinical studies, TOK-001 has demonstrated a novel MOA acting in three distinct ways to treat prostate cancer: as an androgen receptor antagonist, as a CYP17 lyase inhibitor and by decreasing overall androgen receptor levels in prostate cancer cells. TOK-001 is the only drug in development shown to exhibit this property. Importantly, TOK-001 has demonstrated improved efficacy compared with any individual therapy or investigational agent in development to treat prostate cancer.
In November 2009, Tokai announced the initiation of the ARMOR clinical development program for TOK-001 in patients with CRPC. Read more about the ARMOR clinical development program.
