Recent advances in tumor-targeting anticancer drug conjugates.
Traditional cancer chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be a killed by cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing severe undesirable side effects. Therefore, various drug delivery protocols and systems have been explored in the last three decades. Tumor cells overexpress many receptors and biomarkers, which can be used as targets to deliver cytotoxic agents into tumors. In general, a tumor-targeting drug delivery system consists of a tumor recognition moiety and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate. The conjugate, which can be regarded as 'prodrug', should be systemically non-toxic. This means that the linker must be stable in circulation. Upon internalization into the cancer cell the conjugate should be readily cleaved to regenerate the active cytotoxic agent. Tumor-targeting conjugates bearing cytotoxic agents can be classified into several groups based on the type of cancer recognition moieties. This review describes recent advances in tumor-targeting drug conjugates including monoclonal antibodies, polyunsaturated fatty acids, folic acid, hyaluronic acid, and oligopeptides as tumor-targeting moieties.
Jaracz
Stanislav
S
Department of Chemistry and Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Chen
Jin
J
Kuznetsova
Larisa V
LV
Ojima
Iwao
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D018796:Immunoconjugates / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D018796:Immunoconjugates; D006820:Hyaluronic Acid