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Review Article
Volume 1, Article ID: 2025.0004
Nosayba Al-Damook
nosayba.aldamook@aau.ac.ae
Molham Sakkal
mohammad.sakkal@aau.ac.ae
Sedra Kremesh
sedra.kremish@gmail.com
Walaa K. Mousa
walaa.mousa@aau.ac.ae
Mostafa Khair
mrk6@nyu.edu
Ghalia Khoder
gkhoder@sharjah.ac.ae
Rose Ghemrawi
rose.ghemrawi@aau.ac.ae
1 College of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates
2 AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates
3 College of Pharmacy, Mansoura University, Mansoura, Egypt
4 Core Technology Platforms, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, United Arab Emirates
5 Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, UAE
6 Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE
* Author to whom correspondence should be addressed
Received: 30 Jan 2025 Accepted: 11 Apr 2025 Available Online: 14 Apr 2025
Cancer cells sustain rapid growth by reprogramming their metabolism to depend heavily on glycolysis, enhanced insulin signaling, and adaptive changes in the unfolded protein response (UPR). Insulin Potentiation Therapy (IPT) enhances chemotherapy efficacy by increasing insulin receptor expression, which in turn improves the uptake of chemotherapeutic agents. Meanwhile, targeting endoplasmic reticulum (ER) stress disrupts the protein-folding machinery within cancer cells, steering them toward apoptosis. However, IPT faces several limitations, including limited clinical evidence, variable responses across tumor types, and concerns regarding safety and standardization. This review is the first to comprehensively examine the combined modulation of ER stress and IPT, highlighting novel clinical applications and presenting supporting evidence for this synergistic approach in cancer treatment. We compare the distinct metabolic features of cancer cells with those of normal cells and analyze how these differences contribute to tumor progression, the critical role of ER stress in cancer development, and the influence of insulin on cancer metabolism. In addition, we explore the potential synergy between IPT and ER stress modulation by delving into the mechanisms underlying IPT, the benefits of integrating ER stress modulation with IPT, and how insulin can modulate ER stress to improve therapeutic outcomes.
Disclaimer: This is not the final version of the article. Changes may occur when the manuscript is published in its final format.