AR Expression in Breast Cancer CTCs Associates with Bone Metastases

作者：Aceto Nicola; Bardia Aditya; Wittner Ben S; Donaldson Maria C; O'Keefe Ryan; Engstrom Amanda; Bersani Francesca; Zheng Yu; Comaills Valentine; Niederhoffer Kira; Zhu Huili; Mackenzie Olivia; Shioda Toshi; Sgroi Dennis; Kapur Ravi; Ting David T; Moy Beverly; Ramaswamy Sridhar; Toner Mehmet; Haber Daniel A; Maheswaran Shyamala^*

来源：Molecular Cancer Research, 2018, 16(4): 720-727.

DOI：10.1158/1541-7786.MCR-17-0480

Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER) thorn breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ERthorn breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients.
Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer.

• 出版日期2018-4