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A more thorough understanding of molecular alterations in the components of several signaling pathways as new targets for cancer therapy is needed because of current innate restrictions such as drug toxicity, side effects, and acquired or de novo resistance. The PI3K\/Akt\/mTOR pathway is overactivated in many solid tumors, such as breast and ovarian cancers. This pathway in normal cells is essential for growth, proliferation, and survival. However, it is an undesirable characteristic in malignant cells. We have reviewed multiple studies about the effect of melatonin on breast and ovarian cancer, focusing on the PI3K\/Akt\/mTOR pathway. Melatonin exerts its inhibitory effects via several mechanisms. A: Downregulation of downstream or upstream components of the signaling pathway such as phosphatase and tensin homolog (PTEN), phosphatidylinositol (3,4,5)\u2010trisphosphate kinase (PI3K), p\u2010PI3K, Akt, p\u2010Akt, mammalian target of rapamycin (mTOR), and mTOR complex1 (mTORC1). B: Apoptosis induction by decreasing MDM2 expression, a downstream target of Akt, and mTOR, which leads to Bad activation in addition to Bcl\u2010XL and p53 inhibition. C: Induction of autophagy in cancer cells via activating ULK1 after mTOR inhibition, resulting in Beclin\u20101 phosphorylation. Beclin\u20101 with AMBRA1 and VPS34 promotes PI3K complex I activity and autophagy in cancer cells. The PI3K\/Akt\/mTOR pathway overlaps with other intracellular signaling pathways and components such as AMP\u2010activated protein kinase (AMPK), Wnt\/\u03b2\u2010catenin, mitogen\u2010activated protein kinase (MAPK), and other similar pathways. Cancer therapy can benefit from understanding how these pathways interact and how melatonin affects these pathways.<\/jats:p>","DOI":"10.1002\/iub.2900","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T09:36:17Z","timestamp":1725010577000},"page":"1035-1049","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Melatonin effect on breast and ovarian cancers by targeting the <scp>PI3K<\/scp>\/<scp>Akt<\/scp>\/<scp>mTOR<\/scp> pathway"],"prefix":"10.1002","volume":"76","author":[{"given":"Vahid","family":"Pourbarkhordar","sequence":"first","affiliation":[{"name":"Student Research Committee Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohrab","family":"Rahmani","sequence":"additional","affiliation":[{"name":"Student Research Committee Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Roohbakhsh","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Pharmaceutical Research Center, Institute of Pharmaceutical Technology Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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