Irene Olaizola – Investigadora predoctoral en IIS Biodonostia.
IIS Biodonostia - Sala de formación (3ª planta)
Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary malignant tumors with dismal prognosis. Its incidence is increasing globally, and a raising trend of mortality has been reported.
The first-line treatment for advanced CCA [cisplatin (CisPt) and gemcitabine] is considered palliative due to the high chemoresistance of this cancer, barely impacting on patients’ overall survival. Since its approval by the Food and Drug Administration (FDA) in1978, CisPt has become the most widely used chemotherapeutic agent against solid malignant tumors, including CCA.
CisPt is a platinum (Pt) derived compound that induces single-strand DNA breaks, leading to its fragmentation and subsequent cancer dell death. However, cancer cells can activate their DNA repair mechanisms against single-strand DNA breaks, hence, being able to survive and become resistant to CisPt. Therefore, there is an urgent need to find out new alternative therapeutic approaches for CCA aimed at overcoming such chemoresistance.
In our study, we have designed, synthesized and studied a new generation of platinum (Pt)-derived chemotherapeutic drugs (named Aurki-Pt) that produce inter-strand DNA breaks (vs classical single-strand breaks induced by CisPt and related compounds) and thus prevent the development of DNA repair mechanisms in cancer cells.