Targeting mitotic regulators as a therapeutic strategy to overcome chemoresistance in cancer
admin-cespu
Principal Investigator:
Patrícia Silva
Leader Institution:
UNIPRO, IUCS-CESPU
Research Team:
Patrícia Silva, Hassan Bousbaa, Sara Ricardo, Mariana Nunes, Bárbara Pinto, João Silva
Funding entity:
CESPU
Budget:
4500 €
Period covered:
01/09/2025-2026
Abstract:
Paclitaxel (PTX) is a widely used chemotherapeutic drug against solid tumors, but resistance significantly limits its long-term efficacy and, consequently, its clinical success. Key mitotic regulators, such as Aurora B, MPS1, and Eg5, are critical for mitotic fidelity, and their dysregulation has been implicated in tumor progression and PTX resistance. This project aims to investigate their role in chemoresistance by characterizing their expression in PTX-sensitive and PTX-resistant cancer cell lines, and by validating their clinical relevance in primary and metastatic patient tumor samples. We will also assess the therapeutic potential of combining PTX with selective inhibitors targeting these mitotic regulators in resistant cells, evaluating effects on cancer cell viability, mitotic arrest, and apoptosis. By defining expression patterns and testing targeted inhibition strategies, this study seeks to overcome PTX resistance and advance the development of more effective treatments for aggressive cancers.
Paclitaxel (PTX) is a widely used chemotherapeutic drug against solid tumors, but resistance significantly limits its long-term efficacy and, consequently, its clinical success. Key mitotic regulators, such as Aurora B, MPS1, and Eg5, are critical for mitotic fidelity, and their dysregulation has been implicated in tumor progression and PTX resistance. This project aims to investigate their role in chemoresistance by characterizing their expression in PTX-sensitive and PTX-resistant cancer cell lines, and by validating their clinical relevance in primary and metastatic patient tumor samples. We will also assess the therapeutic potential of combining PTX with selective inhibitors targeting these mitotic regulators in resistant cells, evaluating effects on cancer cell
viability, mitotic arrest, and apoptosis. By defining expression patterns and testing targeted inhibition strategies, this study seeks to overcome PTX resistance and advance the development of more effective treatments for aggressive cancers.