Second-Generation Antimitotics in Cancer Clinical Trials

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2021

Autores

Novais, P (Autor) Outra; Silva, PMA (Autor) Outra; Maria Isabel Amorim (Autor) FCUP; Bousbaa, H (Autor) Outra

Revista

Título: Pharmaceutics

Vol. 144

Página Final: 1011

ISSN: 1999-4923

Editora: MDPI

Indexação

ISI Web of Knowledge - 11 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 45