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Pharmacologically Relevant Species: Lessons from Denosumab
A pharmacologically relevant species is an animal in which the drug recognizes its target and produces the intended biological effect. For denosumab, a fully human IgG2 antibody against RANKL, that species turned out to be the cynomolgus monkey, because ordinary mice and rats cannot recognize the antibody’s target at all. The review record shows the full evidence chain: binding, selectivity, functional activity, and in vivo response, with knock-in mice and an OPG-Fc surrogate filling the gaps. Why species selection is the first make-or-break decision In nonclinical development of an antibody, the choice of species is not a logistical detail. It decides whether every later pharmacology and toxicology result can be…
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Understanding Bone Fracture Risk in Prostate Cancer Patients on Androgen Blockade Therapy
Prostate cancer is one of the most common cancers in men. When the disease progresses, doctors often prescribe hormone-based therapies that target the androgens fueling tumor growth. One common approach is maximal androgen blockade (MAB)—combining traditional androgen deprivation therapy (ADT) with drugs that block androgen receptor signaling. These add-on medications include abiraterone acetate, enzalutamide, apalutamide, and darolutamide. Some patients also receive older anti-androgens like flutamide, bicalutamide, or nilutamide. A systematic review and meta-analysis published in early 2026 in Prostate Cancer and Prostatic Diseases asked a straightforward question: does adding these androgen receptor pathway inhibitors to standard hormone therapy increase fracture risk? The research team analyzed 17 clinical trials with more than 16,000 patients…
