Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway

Liu, Qian; Shen, Yutao; Xiong, Yujia; Bai, Jiwei; Zhang, Yazhuo; Li, Chuzhong

doi:10.7150/jca.79726

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J Cancer 2023; 14(1):61-71. doi:10.7150/jca.79726 This issue Cite

Research Paper

Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway

Qian Liu^1#, Yutao Shen^1#, Yujia Xiong¹, Jiwei Bai^1,2, Yazhuo Zhang^1,2✉, Chuzhong Li^1✉

1. Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China.
2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
#These authors have contributed equally to this work and share first authorship.

Citation:

Liu Q, Shen Y, Xiong Y, Bai J, Zhang Y, Li C. Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway. J Cancer 2023; 14(1):61-71. doi:10.7150/jca.79726. https://www.jcancer.org/v14p0061.htm

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Abstract

Total 158 gonadotropin-type pituitary adenoma tissue specimens were collected and the expression of ESR1 in gonadotropin-type pituitary adenoma and its association with the overall survival of patients were analyzed. Transcriptome-sequencing data containing 79 cases of gonadotropin-type pituitary adenoma was used to search for all ESR1-related genes. KEGG pathway enrichment analysis was performed to identify the altering pathway and targeting genes. The in vitro and in vivo pituitary models were used to evaluate the therapeutic efficacy of estrogen receptor (ER) inhibitors AZD9496 and fulvestrant. The mechanism of AZD9496 and fulvestrant in suppressing pituitary adenoma were also investigated. Low-level ESR1 had longer progression-free survival (PFS) in pituitary adenoma patients. ErbB signaling pathway was discovered as the main enriched pathway. Furthermore, the STAT5B gene was identified as a key ESR-1-related gene. The expression of STAT5B was significantly positively correlated with ESR1 expression in the pituitary adenoma. AZD9496, a novel ER inhibitor, exhibited a potent inhibitory effect on the growth of in vitro and in vivo pituitary adenoma cells, and its efficacy is comparable to the classic ER inhibitor, fulvestrant. Mechanically, the AZD9496 and fulvestrant significantly blocked JAK2/STAT5B pathway in GT1-1 cells and xenograft mice. Our results provide substantial evidence for the subsequent clinical use of AZD9496 in the treatment of patients with pituitary adenoma.

Keywords: Pituitary adenoma, Estrogen receptor, JAK2, STAT5B, Brain tumor

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APA

Liu, Q., Shen, Y., Xiong, Y., Bai, J., Zhang, Y., Li, C. (2023). Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway. Journal of Cancer, 14(1), 61-71. https://doi.org/10.7150/jca.79726.

ACS

Liu, Q.; Shen, Y.; Xiong, Y.; Bai, J.; Zhang, Y.; Li, C. Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway. J. Cancer 2023, 14 (1), 61-71. DOI: 10.7150/jca.79726.

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CSE

Liu Q, Shen Y, Xiong Y, Bai J, Zhang Y, Li C. 2023. Comparative Efficacy of AZD9496 and Fulvestrant on the Growth of Pituitary Adenoma via Blocking JAK2/STAT5B Pathway. J Cancer. 14(1):61-71.

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