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Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (PDCs)

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CHEMICAL SOCIETY REVIEWS
卷 50, 期 3, 页码 1480-1494

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ROYAL SOC CHEMISTRY
DOI: 10.1039/d0cs00556h

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  1. EPSRC [EP/P020291/1] Funding Source: UKRI

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Peptides offer versatility in oncology drug discovery, with peptide-drug conjugates showing promise in targeting tumors. Despite limitations such as slow progress and limited oral bioavailability, new approaches have enhanced peptide stability, leading to two molecules on the market and various variations in clinical trials.
Peptides can offer the versatility needed for a successful oncology drug discovery approach. Peptide-drug conjugates (PDCs) are an emerging targeted therapeutic that present increased tumour penetration and selectivity. Despite these advantages, there are still limitations for the use of peptides as therapeutics exemplified through their slow progression to get into the clinic and limited oral bioavailability. New approaches to address these problems have been studied and successfully implemented to enhance the stability of peptides and their constructs. There is great promise for the future of PDCs with two molecules already on the market and many variations currently undergoing clinical trials, such as bicycle-toxin conjugates and peptide-dendrimer conjugates. This review summarises the entire process needed for the design and successful development of an oncology PDC including chemical and nanomaterial strategies to enhance peptide stability within circulation, the function of each component of a PDC construct, and current examples in clinical trials.

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