title: Short peptides interfering with signaling pathways as new therapeutic tools for cancer treatment.
abstract: Short peptides have many advantages, such as low molecular weight, selectivity for a specific target, organelles or cells with minimal toxicity. We describe properties of short peptides, which interfere with communication networks in tumor cells and within microenvironment of malignant gliomas, the most common brain tumors. We focus on ligand/receptor axes and intracellular signaling pathways critical for gliomagenesis that could be targeted with interfering peptides. We review structures and efficacy of organelle-specific and cell-penetrating peptides and describe diverse chemical modifications increasing proteolytic stability and protecting synthetic peptides against degradation. We report results of application of short peptides in glioma therapy clinical trials, their rises and falls. The most advanced examples of therapeutics such as short interfering peptides combined with cell-penetrating peptides that show good effectiveness in disease models are presented. It is foreseen that identification of peptides with better clinical properties may improve their success rates in clinical trials.
authors.affiliation: Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Ellert-Miklaszewska
authors.affiliation: Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.|GLIA Sp.z.o.o., Slominskiego 15/509, 00-195 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Poleszak
authors.affiliation: Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Bozena
authors.initials: B
authors.lastname: Kaminska
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides
keywords: cancer signaling pathways; cancer therapy; cell-penetrating peptides; peptide modifications; protein–protein interactions; short interfering peptides; tumor microenvironment