Second-Generation Antimitotics in Cancer Clinical Trials

• Type: Another Publication in an International Scientific Journal
• Date: 2021

Authors

Novais, P (Author) Other; Silva, PMA (Author) Other; Maria Isabel Amorim (Author) FCUP; Bousbaa, H (Author) Other

Journal

Title: Pharmaceutics

Vol. 144

Final page: 1011

ISSN: 1999-4923

Publisher: MDPI

Indexing

ISI Web of Knowledge - 11 Citations

Other information

Authenticus ID: P-00V-3T2

DOI: 10.3390/pharmaceutics13071011

Abstract (EN): Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitosis, expected to induce cell death. However, resistance, toxicity, and slippage limit the MTA's effectiveness. With the desire to overcome some of the MTA's limitations, mitotic and SAC components have attracted great interest as promising microtubule-independent targets, leading to the so-called second-generation antimitotics (SGAs). The identification of inhibitors against most of these targets, and the promising outcomes achieved in preclinical assays, has sparked the interest of academia and industry. Many of these inhibitors have entered clinical trials; however, they exhibited limited efficacy as monotherapy, and failed to go beyond phase II trials. Combination therapies are emerging as promising strategies to give a second chance to these SGAs. Here, an updated view of the SGAs that reached clinical trials is here provided, together with future research directions, focusing on inhibitors that target the SAC components.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 45