Suppression of estrogen actions in human lung cancer

Estrogen plays a critical role in female reproduction but has also been reported to have important roles in various target tissues expressing estrogen receptor (ER) α and/or ERβ in both male and female. ERs especially ERβ have been demonstrated to be present and functional in both normal human lung and its disorders including cancer. Non-small cell lung carcinomas (NSCLCs) are well-known to be composed of heterogeneous groups. Squamous cell carcinoma is the most common subtype in men, but adenocarcinoma is the most common histologic subtype in women. Therefore, sex steroid hormones such as estrogens have been considered to play some roles in NSCLC. In particular, results of several epidemiological analyses pointed out the association between physiological or artificial alterations of hormone status such as menstruation and postmenopausal administration of hormone replacement therapy and lung cancer risks or its development especially in female subjects. In NSCLC tissues, intratumoral estrogen synthesis via aromatase, which is a key enzyme in the estrogen synthesis involved in aromatization of androgens into estrogens, has recently become of clinical interest as a possible target of therapy. Therefore, in this review, we focused on the potential of an endocrine therapy in NSCLC using clinically available inhibitors of estrogen and aromatase actions.