Anti-mitotic agents: Are they emerging molecules for cancer treatment?
Mutations in cancer cells frequently result in cell cycle alterations that lead to unrestricted growth compared to normal cells. Considering this phenomenon, many drugs have been developed to inhibit different cell-cycle phases. Mitotic phase targeting disturbs mitosis in tumor cells, triggers the spindle assembly checkpoint and frequently results in cell death. The first anti-mitotics to enter clinical trials aimed to target tubulin. Although these drugs improved the treatment of certain cancers, and many anti-microtubule compounds are already approved for clinical use, severe adverse events such as neuropathies were observed. Since then, efforts have been focused on the development of drugs that also target kinases, motor proteins and multi-protein complexes involved in mitosis. In this review, we summarize the major proteins involved in the mitotic phase that can also be targeted for cancer treatment. Finally, we address the activity of anti-mitotic drugs tested in clinical trials in recent years.
Biotechnology Center of the Federal University of Rio Grande do Sul, Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Larissa Siqueira
LS
Penna
Biotechnology Center of the Federal University of Rio Grande do Sul, Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
João Antonio Pêgas
JAP
Henriques
Biotechnology Center of the Federal University of Rio Grande do Sul, Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: diegobonatto@gmail.com.
Diego
D
Bonatto
D000818:Animals; D050256:Antimitotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D050256:Antimitotic Agents; D000970:Antineoplastic Agents
Cancer; Cancer treatment; Clinical trials; Mitosis; Mitotic inhibitors