Depending on the stage of the cancer at diagnosis, surgery and radiation therapy are often important first steps in the treatment of prostate cancer. However, most patients are ultimately placed on a hormone therapy regimen depending on the stage of the cancer. While this treatment will effectively control and halt growth, the prostate cancer cells inevitably grow resistant to androgen therapy (i.e. androgen-independent). Approximately, 40% to 50% of prostate cancer patients will eventually develop androgen-independent prostate cancer, with average survival estimated at just 18 months. Therefore, there is a significant unmet need for new, non-androgen, anti-hormonal strategies for the management of prostate cancer.

Prostate cancer is primarily diagnosed in men over the age of 65, and of those diagnoses, most cases are in advanced stages (stages III or IV). The percentage of patients diagnosed at localized, locally-advanced, and advanced stages is 51%, 22% and 27% respectively. And at each of these stages, patients presenting androgen-independent prostate cancer at diagnosis are 20%, 24% and 42%, respectively. Of these patients initially diagnosed with prostate cancer, the percentage of them developing androgen-independent prostate cancer is 32%, 52% and 79%, respectively. In light of the late diagnoses, many countries have instituted improved screening procedures, resulting in diagnoses at earlier stages. Early detection of prostate cancer will improve prognosis and enhance the efficacy and use of treatments, such as AT-001.

Aside from androgen, relaxin is another hormone implicated in prostate tumor progression. Relaxin hormone antagonists represent a first-in-class treatment to curb tumor growth in prostate cancer. Therefore, relaxin receptor antagonists block relaxin-stimulated tumor and blood vessel growth, and function as an "anti-relaxin" therapy. Unlike anti-androgen therapies, anti-relaxin therapies can potentially be continued once the prostate cancer transitions to an androgen-independent state, and in combination with aggressive chemotherapeutics when prostate cancers become metastatic (Stage III and beyond). The role of relaxin in prostate cancer tumor progression is increased upon the cancer's transition to androgen independence. Frequently-occurring mutations in the tumor-suppressor gene p53 are known to facilitate androgen-independent prostate cancer tumor growth, and the relaxin pathway has been implicated as an agent responsible for driving this process. In effect, relaxin signalling in prostate cancer can drive androgen receptor signalling pathway activation via an intracellular mechanism that is independent of external stimulation by androgens. These findings set out the relaxin pathway as a critical signalling cascade facilitating the growth of both androgen-sensitive and androgen-independent prostate cancer tumors, further highlighting the need for developing drugs targeting this pathway.

Therefore, relaxin antagonists, such as AT-001, offer the potential for patients to continue hormone therapy well beyond the point where prostate cancers become insensitive to traditional anti-androgen therapeutic strategies. Because relaxin has been implicated in several other types of cancers, additional anti-relaxin programs are under development, which may offer utility for other cancer treatments such as for breast and ovarian cancers.


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