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Repurposing failed pharmaceuticals as the first targeted medicines for the treatment and prevention of breast cancer

V Craig Jordan
Published in : HAMDAN MEDICAL JOURNAL ; Vol 7, No 3 (2014)
DOI : 10.7707/hmj.345

Abstract


The selective oestrogen receptor modulators (SERMs) tamoxifen and raloxifene (Evista®, Eli Lilly, Indianapolis, IN, USA) are both pioneering medicines that have improved the health and life expectancy of millions of women around the world. These are targeted therapies to treat or prevent breast cancer by blocking the tumour oestrogen receptor (ER) to prevent oestrogen-stimulated growth but, at the same time, modulate bone to express oestrogen-like effects to prevent fractures. Raloxifene was the first medicine to be approved for the prevention of both breast cancer and osteoporosis; however, both drugs were not initially destined to be developed at all. Tamoxifen was intended to be a contraceptive, and raloxifene was to be a breast cancer drug targeted to tumour ER, but both applications failed. In both cases, drug development was terminated. Nonetheless, the abandoned drugs were repurposed through careful laboratory models of human disease to be resurrected as firstsin their class of targeted medicines. Tamoxifen became the gold standardas the antihormone therapy for prevention and treatment of all stages of breast cancer, in women, ductal carcinoma in situ and male breast cancer. No other medicine has that distinction. Raloxifene was the first SERM to be approved for two completely different diseases, the treatment of osteoporosis and the prevention of breast cancer. These targeted therapies changed medicine.


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