metastatic Castration-Resistant Prostate Cancer

Prostate cancer is one of the top three most frequently occurring cancers and affects around one million men worldwide.

Ten to fifteen per cent of patients develop locally recurrent or metastatic disease which is associated with a significantly reduced survival rate.

For those patients where cancer has proliferated beyond the prostate gland, the standard therapy is androgen deprivation and androgen receptor blockade, as it has been shown that androgen, produced primarily from the testes, drives prostate cancer through the androgen receptors.

need to explain the term castration in this context.

What is castration-resistant prostate cancer?

However, a small percentage of patients, and eventually almost all patients, become resistant to both hormone deprivation and to drugs that block the androgen receptors. This resistance is due to the emergence of AR variants which have lost the ligand binding site targeted by current androgen receptor antagonists.

Initial treatments for advancing prostate cancer focus on reducing the levels of circulating male hormones (androgens) in the body which the tumour requires for growth. Over time, however, the cancer cells are able to circumvent such treatments and can develop into the castration-resistant form of the disease (CRPC). This is lethal with overall survival typically less than 14 months.

The development of CRPC is characterised by the presence of functional but altered androgen receptors, which mediate the effects of male hormones. Current therapies are ineffective in reducing the activity of these altered receptors. 

Dual androgen receptor programme

HOX is evaluating a series of compounds that act as inhibitors of the androgen receptor, collectively referred to as HTL-003.

Read about the dual androgen receptor programme HTL-003 here