Targeting of Progesterone Receptor Membrane Component 1 to Combat Lung Adenocarcinoma
Posted: 19 Feb 2020
Date Written: February 19, 2020
Lung cancer is one of the leading cause of mortality and morbidity globally. It has a 5 year dismal survival rate of less than 15%. In India alone, lung cancer accounts for 9.3% of all cancer-related mortality. Among lung cancer cases 85% accounts for Non-Small Cell Lung Cancer (NSCLC) type. Nevertheless, lung adenocarcinoma represents the major histological form of NSCLC occurrence in 40% of cases. Emerging evidences from literature suggests the involvement of PGRMC1 (Progesterone growth receptor membrane component 1) in lung adenocarcinoma initiation. PGRMC1 is a membrane associated receptor protein which plays a crucial role in regulating myriad pathways related to drug resistance, evasion of cell death, promotion of cell migration, tumorigenesis and cancer progression. It is reported to be significantly up-regulated in variety of tumor’s including thyroid, ovary and breast. Recent literature has also suggested that PGRMC1 is abundant in lung cancer tissues. Correspondingly it is also observed to be having a high correlation with poor patient survival in lung adenocarcinoma cases. Preliminary analysis from our lab by computational approaches (High throughput virtual screening of 30,000 small molecules, molecular docking and ADME analysis) revealed Compound X (CX) as a potential small molecule inhibitor against PGRMC1. CX is a flavonoid with pharmacological properties such as anti-oxidant, anti-inflammatory, anti-hyperglycemic and pro-apoptotic activity in humans. Nevertheless, this will be the first study, proposed to understand its potential efficacy and mechanism of action of CX against lung cancer.
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