Aggressive breast cancers often resist standard therapies due to mechanisms related to both tumour cells and the tumour microenvironment. Many chemotherapeutic drugs increase ceramides, lipids that promote cell death. CERT, a protein involved in ceramide transport, reduces their accumulation; therefore, lowering CERT levels could increase sensitivity to chemotherapy by raising ceramide levels and improving the therapeutic response. This project investigates CERT\u2019s role in treatment resistance and develops new degraders capable of directing CERT directly to the proteasome via Usp14, without relying on E3 ligases. The molecules developed have been validated through chemical synthesis, biochemical characterisation and studies in breast cancer models, providing evidence that CERT is a promising therapeutic target. <\/p>\n","protected":false},"excerpt":{"rendered":"
This project investigates how the CERT protein contributes to chemotherapy resistance in aggressive breast cancer, including interactions with cancer-associated fibroblasts (CAFs), and explores whether reducing CERT can improve the response to treatment. To achieve this, the researchers have developed new PROTAC-based molecules that directly degrade CERT via the proteasome, with the aim of enhancing cancer cell death and validating CERT as a therapeutic target. <\/p>\n","protected":false},"featured_media":11203,"parent":0,"template":"","meta":{"_acf_changed":false},"tags":[174,202],"enfermedad":[171],"framework":[131],"linea-de-investigacion":[172,163],"class_list":["post-11202","proyecto","type-proyecto","status-publish","has-post-thumbnail","hentry","tag-drug-discovery","tag-proteins","enfermedad-cancer","framework-plan-estatal-peicti","linea-de-investigacion-treat","linea-de-investigacion-understand","entry"],"acf":[],"yoast_head":"\n