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.
Highlights
Improving the therapeutic index of anticancer agents is an enormous challenge
The results showed an increase in the anti-proliferative activity of gemcitabine in vitro upon conjugation with the cell-penetrating peptides (CPPs)
Studies conducted on the five mouse pancreatic cancer cell xenograft models showed that the high expression of neuropilin-1 enhanced the anticancer effect of gemcitabine combined with Internalized-RGD ** (iRGD) in comparison with its monotherapy
Summary
Improving the therapeutic index of anticancer agents is an enormous challenge. In a time when the number of patients suffering from a cancer-related disease has been increasing each day and when conventional therapies gather a worrying number of deficits and drawbacks [1,2], new treatment options are required to relieve the symptoms and to eradicate the disease. Likewise, phosphorylated metabolites of gemcitabine are inactivated via the reduction by cellular 5 -nucleotidase (5 -NT) and are rapidly removed from the body by the enzymatic conversion of gemcitabine [30,31] Another important drawback associated with gemcitabine therapy is the drug resistance related to the nucleoside transporter deficiency, which is developed by some tumor cells after the initial tumor regression [32]. For this reason, many approaches have been made to improve the safety profile of gemcitabine and increase its chemotherapeutic index.
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