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Abstract

Colorectal cancer (CRC) is one of the most fatal cancers in the world; acquired chemoresistance and an increasing prevalence of early-onset illness make treatment limited. This review investigates pramlintide, which is used in diabetes management, as a potential for repurposing in CRC treatment. According to the in vitro study on HCT-116 and HT-29 cell lines, the binding of pramlintide to the AMY3 receptors alters tumor glycolysis by inhibiting hexokinase II, thereby decreasing both the Warburg effect and the pentose phosphate pathway. The consequent NADPH depletion increases oxidative stress and makes CRC cells more susceptible to standard chemotherapeutics like oxaliplatin, irinotecan, and 5-fluorouracil. Interestingly, Pramlintide's actions seem to go beyond direct p53 signaling; in p53-mutant HT-29 cells, for recovering apoptotic competence, pramlintide may activate the structurally related p63 and p73 pathways; however, HT-29 consistently exhibits lower sensitivity and needs greater dosages than HCT-116. The review further considers how pramlintide interacts with AMPK-driven autophagy, how it differs mechanistically from metformin, and how hyperglycemia-driven PI3K/Akt/mTOR signaling affects chemotherapy response

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