Androgen receptor degradation may circumvent common drug resistance in advanced prostate cancer
Selective Androgen Receptor Degraders are a novel class of drugs. The binding of the androgen receptor (AR) is a major driver of prostate tumor cell proliferation, and blocking the androgen receptor to prevent its activation is a major target for anti-tumor drugs. In many cancer patients, tumor cells will continue to respond to this hormone binding by failing to proliferate. However, the binding of a drug to the receptor to block its activity can, over time, change (through a mutation) to result in the receptor binding causing activation rather than inhibition of tumor growth.
SARDs are designed to not only bind to androgen receptors, but also induce androgen receptor degradation and ultimately inhibit tumor cell proliferation in androgen-dependent prostate cancer cell lines. These results suggest that selective AR degradation (caused by a SARD) may be an effective therapeutic prostate tumor strategy where a mutated AR can be degraded by the SARD. This ability to circumvent common drug resistance in prostate cancer patients by this new class of drug may provide an important tool for effective new treatments.