Gemcitabine Peptide-Based Conjugates and Their Application in Targeted Tumor Therapy

Abstract

A major obstacle in tumor treatment is associated with the poor penetration of a therapeutic agent into the tumor tissue and with their adverse influence on healthy cells, which limits the dose of drug that can be safely administered to cancer patients. Gemcitabine is an anticancer drug used to treat a wide range of solid tumors and is a first-line treatment for pancreatic cancer. The effect of gemcitabine is significantly weakened by its rapid plasma degradation. In addition, the systemic toxicity and drug resistance significantly reduce its chemotherapeutic efficacy. Up to now, many approaches have been made to improve the therapeutic index of gemcitabine. One of the recently developed approaches to improve conventional chemotherapy is based on the direct targeting of chemotherapeutics to cancer cells using the drug-peptide conjugates. In this work, we summarize recently published gemcitabine peptide-based conjugates and their efficacy in anticancer therapy.

Whether cytidine deaminase of Mycoplasma hyorhinis promotes drug resistance by decomposing gefitinib

“…By analyzing the chemical structure of cytosine, cytidine and gemcitabine, CDA converts the amino group to the carboxyl group of pyrimidine ring in gemcitabine, resulting in the inactivated product dFdU [24][25][26][27].…”

HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells

“…Treatment with FOLFIRINOX has been associated with enhanced patient survival but also with increased toxicity relative to treatment with gemcitabine [ 36 ]. Modifications to gemcitabine are currently being studied to improve its effects, such as the covalent binding of gemcitabine to cardiolipin or gemcitabine peptide-based conjugates that enhance its incorporation into cells and improve its effects as an anti-cancer therapy [ 37 , 38 ]. The high mortality and aggressive nature of pancreatic cancer, the challenges of early detection and consequently, their high rate of metastasis, in conjunction with a lack of effective treatments to control the tumor if surgical resection fails, are together responsible for the clinical significance of pancreatic cancers.…”

Peptide–drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

“…Carboxymethyl chitosan/poly (amidomethylamine) (CMCht/PAMAM) dendrimer nanoparticles can form specific delivery vehicles through a short peptide conjugation with gemcitabine. YIGSR peptide conjugated dendrimer peptides are selective for HCT-116 cells with LR (Leptin receptor) 46 . Gemcitabine was released intracellularly which led to cell death 47 .…”