hormonerefractory

Hormonerefractory, or hormone-refractory, describes tumors that no longer respond to hormonal therapy designed to slow or halt growth by suppressing hormone signaling. The term is most commonly applied to prostate cancer, where tumors that were initially driven by androgens continue to grow despite achieving castrate levels of testosterone. In German medical literature, hormonrefraktär is used similarly and may be paired with terms such as castration-resistant to emphasize resistance at low testosterone levels.

Mechanisms of resistance are diverse. Prostate cancer cells can maintain androgen receptor signaling despite low hormone levels through AR gene amplification, mutations, or alternative splice variants. Tumors may increase intratumoral androgen synthesis, bypass signaling pathways, or undergo lineage changes such as neuroendocrine differentiation. Other pathways, including PI3K/AKT and MAPK, may contribute to continued growth independent of androgen signaling. The term can also apply to other hormone-driven cancers when they cease to respond to endocrine therapies.

Diagnosis relies on clinical and laboratory criteria. In prostate cancer, progression is typically defined by radiographic evidence of growth or new lesions and/or rising PSA levels despite castrate testosterone (<50 ng/dL). Imaging and biomarker trends help establish refractoriness and guide subsequent treatment.

Management emphasizes sequential systemic therapies and symptom control. Options commonly include next-line androgen receptor pathway inhibitors, chemotherapy (e.g., taxanes), PARP inhibitors in selected molecular contexts, radiopharmaceuticals for bone metastases, and bone-targeted therapies. Immunotherapy and combination strategies, as well as ongoing clinical trials, may also be considered. Prognosis varies with tumor biology and treatment responsiveness; advances in targeted therapies have improved survival for some patients with hormone-refractory disease.