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Tumor specifically internalizing peptide ‘HN-1’: Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis

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World Journal of Clinical Oncology 2022年第5期13卷 323-338页

作者： Frank-Un Hong Miguel Castro klaus linse Research&Development Bio-SynthesisInc.LewisvilleTX 75057United States

BACKGROUND Less than 0.5%of intravenously injected drugs reach tumors,contributing to side *** limit damage to healthy cells,various delivery vectors have been formulated;yet,previously developed vectors suffer from poor penetration into solid *** issue was resolved by the discovery of HN-1 peptide isolated via biopanning a phage-display ***-1 targets human head and neck squamous cell carcinoma(HNSCC)(breast,thyroid;potentially lung,cervix,uterine,colon cancer),translocates across the cell membrane,and efficiently infiltrates solid ***-1 peptide has been conjugated to various anticancer drugs and imaging agents though the identity of its receptor remained *** To decipher the clues that pointed to retinoblastoma(Rb)-regulated discoidindomain receptor 1 as the putative receptor for HN-1 is *** HN-1 peptide was synthesized and purified using reverse-phase highperformance liquid chromatography and gel *** predicted mass was confirmed by mass *** image the 3-dimensional structure of HN-1 peptide,PyMOL was *** modeling was also performed with PEP-FOLD3 software via RPBS bioinformatics web portal(INSERM,France).The immunohistochemistry results of discoidin domain receptor 1(DDR1)protein were obtained from the publicly accessible database in the Human Protein Atlas portal,which contained the images of immunohistochemically labeled human cancers and the corresponding normal *** The clues that led to DDR1 involved in metastasis as the putative receptor mediating HN-1 endocytosis are the following:(1)HN-1 is internalized in phosphate-buffered saline and its uptake is competitively inhibited;(2)HN-1(TSPLNIHNGQKL)exhibits similarity with a stretch of amino acids in alpha5 beta3 integrin(KLLITIHDRKEF).Aside from two identical residues(Ile-His)in the middle,the overall distribution of polar and nonpolar residues throughout the sequences is nearly *** HN-1 sequence lacks

关键词： HN-1 peptide Solid tumor Targeted drug delivery Discoidin domain receptor 1 Tyrosine kinase Metastasis

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Tumor-specific lytic path“hyperploid progression mediated death”:Resolving side effects through targeting retinoblastoma or p53 mutant

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World Journal of Clinical Oncology 2020年第11期11卷 854-867,I0001页

作者： Frank-Un Hong Miguel Castro klaus linse Department of Research and Development Bio-SynthesisLewisvilleTX 75057United States

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path“hyperploid progression-mediated death”targeting retinoblastoma(Rb)or p53-mutants defective in G1 DNA damage *** genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb *** encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases.A 3Dstructure of Rb dimer is shown,confirming its multimeric *** assumes a central role in cell cycle regulation and the“Rb pathway”is universally inactivated in human *** refers to a state in which cells contain one or more extra *** progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer *** evidence for the triggering of hyperploid progression-mediated death in RBmutant human retinoblastoma cells is ***,the very genetic mutation that predisposes to cancer can be exploited to induce *** discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic *** triggering the lytic path,targeted therapy with tumor specificity at the genetic level can be *** sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.

关键词： Retinoblastoma protein P53 protein Cancer Checkpoint Taxol Tumorspecific lytic path

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