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MechanoResistance

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Overcoming Mechanically-Induced Resistance to Chemo-Immunotherapy in Pancreatic...

Overcoming Mechanically-Induced Resistance to Chemo-Immunotherapy in Pancreatic Cancer Cancer progression is closely associated with generation of mechanical stresses that cause the compression of tumor vessels, drastically reducing delivery of drugs. My co-workers and I found that host cells and extracellular matri... ver más

31/03/2030

UCY

3M€

Presupuesto del proyecto: 3M€

Líder del proyecto

UNIVERSITY OF CYPRUS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2025-04-01

ERC-2023-ADG: ERC ADVANCED GRANTS Scope:Objectives

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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UCY

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Duración del proyecto: 59 meses Fecha Inicio: 2025-04-01
Fecha Fin: 2030-03-31

Líder del proyecto

UNIVERSITY OF CYPRUS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 3M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cancer progression is closely associated with generation of mechanical stresses that cause the compression of tumor vessels, drastically reducing delivery of drugs. My co-workers and I found that host cells and extracellular matrix in tumors generate these stresses. Furthermore, we identified the anti-hypertensive losartan to alleviate intratumoral stresses and decompress vessels, allowing drugs to enter the tumor. My colleagues tested losartan in pancreatic cancer patients and found improved responses to chemo-radiation. Nonetheless, losartan cannot alleviate all stresses, and my preliminary data indicate that they induce chemotherapy resistance (“mechanoresistance”). Thus, even though vessel decompression facilitates drugs entering the tumor, mechanoresistance renders cancer cells insensitive to drugs. Alleviating mechanoresistance is an urgent clinical need, but this mechanism has not been well studied and strategies to overcome it have not been developed successfully. To address this challenge, I will employ a mixture of cutting-edge bioengineering and biology methods to identify the intracellular mechanisms that promote mechanoresistance, using in vitro and mouse models of pancreatic cancer. I will then employ inhibitors/drugs of the identified mechanisms to overcome mechanoresistance in vitro and in vivo to determine if they increase the efficacy of chemotherapy. I will also confirm whether these drugs work more effectively with losartan or alone. Using the best performing regimen, I will assess the immunological effects and efficacy in combination with immunotherapy, which has yet to induce a benefit in pancreatic cancer trials. In parallel, in order to take this ground-breaking goal of improving pancreatic cancer therapy to the clinic, I will examine the existence of the same mechanoresistance mechanisms in human tumors. The project will introduce novel, patient-specific, therapeutic strategies to directly boost clinical trials in pancreatic cancer patients.

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