What is the Origin of Castration-Resistant Prostate Cancer (CRPC)?

The terminology is clinical, arising from the observation that prostate cancer, while initially androgen-sensitive and responsive to surgical or medical castration, eventually develops resistance. The term "castration-resistant" was introduced to accurately reflect the biological reality that the tumor continues to proliferate without the need for high levels of testicular androgens. This classification is fundamental for guiding subsequent treatment decisions in oncology.

What is the Mechanism of Castration-Resistant Prostate Cancer (CRPC)?

The resistance mechanism is primarily centered on the persistent activity of the androgen receptor (AR) signaling pathway, despite low circulating testosterone. Cancer cells employ several compensatory strategies, including AR gene amplification, AR mutations that allow activation by non-androgen ligands, or the intratumoral synthesis of androgens from adrenal precursors. These molecular adaptations bypass the effects of systemic androgen deprivation, allowing the malignant cells to maintain their growth advantage.

Castration-Resistant Prostate Cancer (CRPC)

Meaning

Castration-Resistant Prostate Cancer, or CRPC, is a critical stage of prostate cancer where the disease progresses despite achieving castrate levels of serum testosterone, typically below 50 ng/dL. This diagnosis signifies that the cancer cells have adapted to grow and multiply even in a severely androgen-deprived environment. CRPC represents a significant clinical challenge, requiring advanced therapeutic strategies beyond standard androgen deprivation therapy.