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Peptide-based therapeutics can potentially bridge the gap between small molecules and protein biologics, combining drug-like properties with the ability to bind to clinical targets with high affinity and selectivity. The clinical targets discussed in this chapter include extracellular targets being developed for in vivo tumor imaging and drug delivery. The chapter includes a section on key intracellular targets with a focus on protein–protein interactions (PPI) mediating cellular signalling pathways that are frequently dysregulated in oncological diseases. These intracellular PPIs comprise the ″un-druggable″ space that is largely inaccessible to current therapeutic molecules but can be targeted by peptide-based therapeutic agents. The chapter discusses the current advancements and chemical approaches to stabilizing active peptide conformations, enabling cellular uptake and intracellular activity. The chapter covers both natural and synthetic rationally designed peptides being developed as therapeutic agents for imaging, drug delivery, vaccines and therapy.

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