van Boxtel W, Verhaegh GW, van Engen-van Grunsven IA, et al. - Given that in androgen receptor-positive (AR+) salivary duct carcinoma (SDC), androgen deprivation therapy (ADT) is first-line palliative treatment, and response rates are 17.6–50.0%. Researchers here examined the predictive value of potential primary ADT resistance mechanisms for clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving palliative ADT (n = 30). The patients with clinical benefit from ADT indicated significantly higher SRD5A1 expression levels and AR pathway activity scores vs those noted for patients without benefit. As per survival analysis, patients with high SRD5A1 expression levels and high AR pathway activity scores had a trend toward a longer median progression-free survival. Further, in an independent cohort of locally advanced SDC patients receiving adjuvant ADT (n = 14), the AR pathway activity analysis, and not SRD5A1 expression, indicated a trend toward better disease-free survival after surgical tumor resection, and in most cases a neck dissection (13/14 patients) and postoperative radiotherapy (13/14 patients). In this work, for the first time, AR pathway activity was suggested to be predictive of clinical benefit from ADT in SDC patients, however, validation is required in a prospective study.