Enhancing Taxol Effectiveness through Targeted Modulation of the Cancer Tubulin Code

Sonia Silva.

i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto - Associação, Portugal.

Taxanes are highly effective chemotherapy drugs, particularly in combination therapies. However, resistance and metastasis limit their effectiveness, especially in aggressive breast cancers such as triple-negative breast cancer. This project aims to develop a new treatment strategy that enhances taxane effectiveness while reducing side effects.

Taxanes disrupt microtubule function, which is often altered in cancer cells. The project builds on previous work on "tubulin code", a regulatory mechanism that generates microtubule diversity through genetic variants and post-translational modifications of tubulins, the proteins that form microtubules. The team has shown that inhibiting a key enzyme involved in tubulin tyrosination makes cancer cells more sensitive to taxanes. The project therefore aims to develop a first-in-class inhibitor of this enzyme to potentiate taxane cytotoxicity, alongside a predictive biomarker to identify the patients most likely to benefit.

If successful, the project could provide a new treatment option for people with high-risk breast cancer, as well as help clinicians select the most effective therapy for each patient.

• Maria Fernanda Martins Borges, RISE-Health, Universidade do Porto, Portugal.

STAGE 2