title: Antibody-DM1 conjugates as cancer therapeutics.
abstract: Synthetic derivatives of the microtubule-targeted agent maytansine, commonly known as drug maytansinoids or DMs, are emerging as potential cancer therapeutics. DM1 is an antibody-conjugatable maytansinoid that was developed to overcome systemic toxicity associated with maytansine and to enhance tumor-specific delivery. Antibody-DM1 conjugates showed promising results in preclinical and clinical evaluations. However, the molecular mechanism of the drug component DM1 was largely unknown. Recently, researchers have examined the mechanism of DM1 at molecular and cellular levels. According to their findings, DM1 binds at the tips of microtubules and suppresses the dynamicity of microtubules. The antibody-DM1 conjugate cleaves inside cells and releases the active drug in a time-dependent manner. The suppression of microtubule dynamics by DM1 induces mitotic arrest and cell death.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, and the Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA. manu.lopus@lifesci.ucsb.edu
authors.forename: Manu
authors.initials: M
authors.lastname: Lopus
mesh_terms: D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D008453:Maytansine