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Second-Generation Antimitotics in Cancer Clinical Trials

Pedro Novais1,2,3, Patrícia M A Silva1, Isabel Amorim4

  • 1CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal.

Pharmaceutics
|August 10, 2021
PubMed

Insights

Second-generation antimitotics targeting the spindle assembly checkpoint (SAC) show promise for cancer therapy. Combination therapies may enhance the efficacy of these microtubule-independent agents, overcoming resistance and toxicity limitations.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Mitosis is a key target for blocking cancer cell proliferation.
  • Classical antimitotics (microtubule-targeting agents, MTAs) are effective but face resistance and toxicity.
  • Second-generation antimitotics (SGAs) target microtubule-independent pathways, including spindle assembly checkpoint (SAC) components.

Purpose of the Study:

  • To provide an updated overview of SGAs that have entered clinical trials.
  • To explore future research directions for SGAs, particularly those targeting SAC components.
  • To highlight the potential of combination therapies for enhancing SGA efficacy.

Main Methods:

  • Review of clinical trial data for SGAs.
  • Analysis of preclinical assay outcomes for mitotic and SAC inhibitors.
  • Literature review focusing on microtubule-independent antimitotic strategies.

Main Results:

  • Many SGAs targeting mitotic and SAC components have shown preclinical promise.
  • Most SGAs entering clinical trials demonstrated limited efficacy as monotherapy, failing to progress beyond Phase II.
  • Combination therapies are emerging as a strategy to improve SGA effectiveness.

Conclusions:

  • SGAs targeting SAC components represent a promising avenue for cancer treatment.
  • Overcoming limitations of MTAs requires novel strategies like microtubule-independent inhibition.
  • Combination therapies are crucial for realizing the full therapeutic potential of SGAs.
Keywords:
antimitoticscancerclinical trialsmitotic slippagespindle assembly checkpoint

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