Introduction: Integrins, which are heterodimeric membrane glycoproteins, consist of a family of cell-surface receptors mediating cell-matrix and cell-cell adhesion. Analysis of tumor-associated integrins has revealed an important relationship between integrins and tumor development, bringing new insights into integrin-based cancer therapies. Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide and integrins appeal to be a novel group of potential therapeutic targets for HCC.
Areas Covered: This review summarizes the current knowledge of integrins involved in HCC and the potential of integrin-targeted drugs in HCC therapy. A brief introduction on the structure, biological function and regulatory mechanism of integrins is given. The distinct expression patterns and biological functions of HCC-associated integrins are described. Finally, the current situation of integrin-based therapies in HCC and other tumor types are extensively discussed in the light of their implications in preclinical and clinical trials.
Expert Opinion: To date, increasing numbers of integrin-targeted drugs are undergoing development and they exhibit diverse effects in cancer clinical trials. Tumor heterogeneity should be emphasized in developing effective integrin-targeted drugs specific for HCC. A better understanding of how integrins cooperatively function in HCC will assist in designing more successful integrin-targeted therapeutic drugs and corresponding approaches.
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http://dx.doi.org/10.1517/14728222.2011.555402 | DOI Listing |
ACS Cent Sci
December 2024
Leiden Institute of Chemistry, Universiteit Leiden, Einsteinweg 55, 2333 CC Leiden, Netherlands.
The blood-brain barrier (BBB) presents one of the main obstacles to delivering anticancer drugs in glioblastoma. Herein, we investigated the potential of a series of cyclic ruthenium-peptide conjugates as photoactivated therapy candidates for the treatment of this aggressive tumor. The three compounds studied, , , and ([Ru(Phphen) Ac-XRGDX-NH)]Cl with Phphen = 4,7-diphenyl-1,10-phenanthroline and X, X = His or Met), include an integrin-targeted pentapeptide coordinated to a ruthenium warhead via two photoactivated ruthenium-X bonds.
View Article and Find Full Text PDFPLoS One
September 2024
Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
Front Pharmacol
March 2024
Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine-Georgia Campus, Suwanee, GA, United States.
Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells preferentially in the bone marrow. Currently, emerging chemotherapy drugs with improved biosafety profiles, such as immunomodulatory agents and protease inhibitors, have been used in clinics to treat MM in both initial therapy or maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT). We previously discovered that caffeic acid phenethyl ester (CAPE), a water-insoluble natural compound, inhibited the growth of MM cells by inducing oxidative stress.
View Article and Find Full Text PDFBioconjug Chem
October 2023
Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, North Carolina 27101, United States.
A synthetic platform has been developed that provides access to platinum(IV) prodrugs of highly cytotoxic platinum-acridine anticancer agents and allows them to be incorporated into conjugation-ready prodrug-payloads (PPLs). The PPLs can be conveniently assembled in highly efficient microscale reactions utilizing strain-promoted azide-alkyne cycloaddition chemistry. Model reactions were performed to study the stability of the PPLs in buffers and media and to assess their compatibility with cysteine-maleimide Michael addition chemistry.
View Article and Find Full Text PDFJ Am Chem Soc
July 2023
Leiden Institute of Chemistry, Universiteit Leiden, Einsteinweg 55, 2333 CC Leiden, Netherlands.
To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Phphen)(OH)], was conjugated to the RGD-containing Ac-MRGDH-NH peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[]Cl and Δ-[]Cl. In the dark, the ruthenium-chelating peptide had a triple action.
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