Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 11; p. 2916
• Main Authors: Hsin, I-Lun, Shen, Huang-Pin, Chang, Hui-Yi, Ko, Jiunn-Liang, Wang, Po-Hui
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.10.2021; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Autophagy; Autophagy - drug effects; c-Myc; c-Myc protein; Cancer; Cell culture; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell Death - drug effects; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Clinical trials; dual PI3K/mTOR inhibitor; Endometrial cancer; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrium; Feedback; Feedback, Physiological; Female; Flow cytometry; Glucose; Growth factors; Humans; Kinases; Microscopy; Models, Biological; mutant p53; Mutant Proteins - metabolism; Myc protein; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Phosphatidylinositol 3-Kinases - metabolism; Phosphoinositide-3 Kinase Inhibitors - pharmacology; PQR309; Proteomes; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-myc - metabolism; PTEN protein; R&D; Research & development; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumor cell lines; Tumor Suppressor Protein p53 - metabolism; Minneapolis Minnesota; St Louis Missouri; United Kingdom > UK; Asia; United States > US; Taiwan; Israel; endometrial cancer; mutant p53; dual PI3K/mTOR inhibitor; PQR309; c-Myc

Gene mutations in PIK3CA, PIK3R1, KRAS, PTEN, and PPP2R1A commonly detected in type I endometrial cancer lead to PI3K/Akt/mTOR pathway activation. Bimiralisib (PQR309), an orally bioavailable selective dual inhibitor of PI3K and mTOR, has been studied in preclinical models and clinical trials. The a...