Chemical chaperones are small molecules that assist proteins in folding correctly, thereby reducing misfolding and aggregation.
-Cancer cells often exhibit high levels of protein synthesis and stress on the protein-folding machinery (such as the endoplasmic reticulum, ER). Misfolded proteins can lead to ER stress and activate the unfolded protein response (UPR). Chemical chaperones can help alleviate this stress by assisting in proper protein folding and reducing aggregation, potentially affecting the survival and proliferation of cancer cells.
-4-Phenylbutyric acid (4-PBA): One of the most extensively studied chemical chaperones, 4-PBA has been researched for its ability to reduce ER stress in various cellular models, including cancer.
-Tauroursodeoxycholic acid (TUDCA): Another chemical chaperone that has been investigated for similar properties in alleviating ER stress.
-Challenges: The dual role of the UPR in both cell survival and death means that the context of treatment is crucial. Moreover, systemic administration of chemical chaperones might affect normal tissues, so selectivity and dosing become important considerations.
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