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proCOLON

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First-in-class beta-catenin inhibitor as treatment for colorectal cancer

With more than 1.9 million new cases and 935,000 related deaths in 2020, colorectal cancer (CRC) is the third most common cancer in men and the second in women. While surgery is the main treatment option for lower grade CRC, patie... ver más

31/10/2023

STICHTING VU

150K€

Presupuesto del proyecto: 150K€

Líder del proyecto

STICHTING VU No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-10-31

ERC-2022-POC1: ERC PROOF OF CONCEPT GRANTS1 Objective:Objectives:

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Cerrada hace 3 años

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1 Participantes

STICHTING VU

150.00K€ | Lider

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Duración del proyecto: 18 meses Fecha Inicio: 2022-04-07
Fecha Fin: 2023-10-31

Líder del proyecto

STICHTING VU No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 150K€

Descripción del proyecto With more than 1.9 million new cases and 935,000 related deaths in 2020, colorectal cancer (CRC) is the third most common cancer in men and the second in women. While surgery is the main treatment option for lower grade CRC, patients with unresectable lesions are treated with chemotherapy. Related therapies are associated with severe drawbacks, such as systemic toxicity, low response rate, and unpredictable resistance. Molecular targeted therapies have emerged as a promising strategy to specifically target cancer cells. For CRC, the inhibition of the Wnt signalling pathway has moved into the focus of novel therapeutic approaches as it is hyperactivated in 80% of all cases. Within the pathway, the protein beta-catenin is considered a particularly attractive target. However, classic small molecule targeting strategies have failed to provide any approved drugs that inhibit beta-catenin so far. We have identified a family of peptidomimetic agents that bind beta-catenin and inhibit its interaction with the TCF/LEF transcription factors. For the first time, it was possible to obtain a crystal structure of a synthetic molecule bound to a therapeutically very attractive site on beta-catenin. In addition, we have confirmed cellular activity of these inhibitors verifying selective inhibition of the Wnt signalling pathway. These findings provide the ideal starting point for the development of novel therapeutics for Wnt-dependent cancers, in particular for CRC. These first-in-class inhibitors will provide the basis for the development of therapeutics that selectively inhibit oncogenic Wnt signalling thereby affecting the viability of corresponding cancer cells. This can enable targeted therapies for Wnt-dependent forms of CRC.

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