Deciphering the mechanisms of action of progesterone in breast cancer
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Gaurav Chakravorty1,2, Suhail Ahmad1,2, Mukul S. Godbole3, Sudeep Gupta2,4, Rajendra A. Badwe2,5 and Amit Dutt1,2
1 Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, Maharashtra, India
2 Homi Bhabha National Institute, Training School Complex, Mumbai 400094, Maharashtra, India
3 Department of Biosciences and Technology, Faculty of Sciences and Health Sciences, Dr. Vishwanath Karad MIT World Peace University, Pune 411038, Maharashtra, India
4 Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Navi Mumbai 410210, Maharashtra, India
5 Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Navi Mumbai 410210, Maharashtra, India
|Amit Dutt,||email:||[email protected]|
Keywords: breast cancer; progesterone;
Received: April 13, 2023 Accepted: May 27, 2023 Published: July 01, 2023
A practice-changing, randomized, controlled clinical study established that preoperative hydroxyprogesterone administration improves disease-free and overall survival in patients with node-positive breast cancer. This research perspective summarizes evidences from our studies that preoperative hydroxyprogesterone administration may improve disease-free and overall survival in patients with node-positive breast cancer by modulating cellular stress response and negative regulation of inflammation. Non-coding RNAs, particularly DSCAM-AS1, play a regulatory role in this process, along with the upregulation of the kinase gene SGK1 and activation of the SGK1/AP-1/NDRG1 axis. Progesterone-induced modification of the progesterone receptor and estrogen receptor genomic binding pattern is also involved in orchestrating estrogen signaling in breast cancer, preventing cell migration and invasion, and improving patient outcomes. We also highlight the role of progesterone in endocrine therapy resistance, which could lead to novel treatment options for patients with hormone receptor-positive breast cancer and for those who develop resistance to traditional endocrine therapies.
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