Cyclotides is a rapidly growing class of plant‐derived cyclic peptides exhibiting several bioactivities with potential applications in the agricultural and pharmaceutical sectors. Both natural and grafted cyclotides have shown promise in cancer therapy. Approximately 70 natural cyclotides belonging to three plant families (Fabaceae, Rubiaceae, and Violaceae) have shown cytotoxicity against several cancer cell lines. Cyclotides exhibit considerable stability against thermal and enzymatic proteolysis, owing to their unique structure with knotted topology and head to tail cyclization. Further, their small size, high stability, oral bioavailability, and tolerance to amino acid substitution in structural loops make them an ideal platform for designing peptide‐based drugs for cancer. Thus, cyclotides provide ideal scaffolds for bioactive epitope grafting and facilitating drug delivery in cancer treatment. Many anticancer linear peptides have been grafted in cysteine knotted cyclic framework of cyclotide for enhancing their cell permeability across cellular membranes, thereby improving their delivery and pharmacokinetics. The present review comprehensively discusses the distribution, toxicity, and anticancer bioactivity of natural cyclotides. Further, it systematically elaborates on the role and action of epitopes' into grafted cyclotides in targeting cancer. The review also encompasses related patents landscape study and future challenges in peptide‐based cancer therapy.
Rise in incidence of various cancers and growing adoption of biological therapy to avoid side effects of conventional cancer therapies is driving the growth of the cancer biotherapy market globally. One such therapy available for the treatment of certain tumors employs arginine-lowering enzymes (ALEs). Several patents have been filed in this technology domain, and many Phase I/II clinical trials of the ALEs especially arginine deiminase (ADI) are underway. Areas covered: Patents and clinical trials in the domain of ALEs for the treatment of cancer were studied with an objective to understand technology trends, targeted areas, key players, and inventors involved. Expert opinion: Amongst the various ALEs, ADI is the most promising enzyme for cancer therapy. ADI-based cancer therapy holds potential in treating liver, skin, lung, gastrointestinal, and blood cancer. ADI-PEG20 has proved to be very effective when used as a component of combination therapy in a first-line treatment. Polaris Group holds the worldwide rights for ADI-PEG20 and is the leading player in developing ADI as a therapeutic agent. Many clinical studies, especially in a combinatorial approach, are underway whose success will pave the way for ADI-PEG to the multimillion cancer market.
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