Targeting the Polycomb Machinery in BAP1-related Pathologies

Projektinformationen

T-BAP

ID Finanzhilfevereinbarung: 101111993

DOI

10.3030/101111993

Projekt abgeschlossen

EK-Unterschriftsdatum 6 Dezember 2023

Startdatum 1 Januar 2024

Enddatum 30 Juni 2025

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy

Periodic Reporting for period 1 - T-BAP (Targeting the Polycomb Machinery in BAP1-related Pathologies)

Berichtszeitraum: 2024-01-01 bis 2025-06-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Cancer treatment is becoming more effective thanks to the growing number of therapeutic options available. Because cancers are highly diverse and can adapt to treatment, doctors need a wide range of strategies to select the best approach for each patient. This is the foundation of precision medicine, where treatments are tailored to the specific characteristics of a patient’s disease.

A new class of therapies, known as targeted degradative approaches, is opening exciting opportunities. Unlike conventional drugs that mainly block enzymatic activity, these approaches can also eliminate proteins that do not have enzymatic functions. This greatly expands the number of disease-related proteins that could potentially be targeted, offering additional hope for patients.

This project builds on this innovative concept by focusing on cancers with mutations in a gene called BAP1, which frequently occurs in certain tumor types. This is based on the identification of a specific weakness, or “molecular vulnerability,” in the way these cancers rely on protein complexes known as Polycomb Repressive Complexes. By exploiting this weakness, the project aims to develop new compounds that could one day become effective treatments for a defined group of cancer patients carrying BAP1 mutations.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

This project has generated new structural insights that form the basis for identifying compounds with potential to be developed into targeted degradative therapies against Polycomb activity. Among the main achievements are the creation of structural models in the presence of natural nucleosomal substrates and the generation of topological data to support advanced structural modelling. These efforts produced a medium-resolution model which, while not yet sufficient to pinpoint high-confidence binders, provides a strong foundation for their future discovery.
Beyond these technical advances, the project’s validation activities demonstrated that this therapeutic approach is not limited to cancers carrying BAP1 mutations. Instead, its potential extends to a wider range of tumor types. This significantly increases both the possible clinical impact and the commercial value of the results. In parallel, the project has undertaken intensive intellectual property management and market exploitation activities

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The project has established the foundation for the future development of novel therapeutic compounds targeting cancers with specific BAP1 mutations. Intensive intellectual property management and exploitation activities have already highlighted the strong commercial potential of this concept, ensuring a solid basis for its further development.

A key step toward identifying high-confidence compounds with clinical and commercial value is the generation of high-resolution structural data. The project has successfully optimized the conditions needed to achieve this outcome, marking an important milestone. However, additional effort and investment are required to reach the next stage. These will be essential to secure the discovery of effective compounds and to ensure the successful translation of the project’s results into both commercial opportunities and tangible clinical benefit for patients.