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Mechano-modulation of tumor microenvironment with mechanotherapeutics and sonopermeation to optimize nano-immunotherapy

Project description

Synergistic strategies for reversing vascular compression in cancer

In certain types of cancer, blood vessels endure compression due to stiffness caused by the intricate interactions between cancer cells and the tumour microenvironment. This leads to reduced blood flow, compromising drug delivery and effectiveness, as well as helping cancer cells evade immune responses. Funded by the European Research Council, the MMSCancer project proposes to combine strategies that mechanically modulate the tumour microenvironment. The synergistic effect of mechanotherapeutics and ultrasound sonopermeation is expected to improve drug delivery through impermeable tumours. Researchers will employ both computational modelling and experimentation to improve the methodology of these strategies.

Objective

Inefficient drug delivery to tumors can reduce dramatically treatment efficacy and thus, affect negatively the life of cancer patients. This is particularly evident in desmoplastic cancers where interactions among cancer cells, stromal cells and the fibrotic matrix cause tumor stiffening and accumulation of mechanical forces that compress tumor blood vessels. Indeed, in subsets of pancreatic cancers and sarcomas, 95% of intratumoral blood vessels may be compressed and up to 80% totally collapsed leading to reduced blood flow (hypo-perfusion) and drug delivery. Hypo-perfusion also leads to hypoxia that helps cancer cells evade the immune system and increase their invasive and metastatic potential. Use of mechanotherapeutics and ultrasound sonopermeation are two mechano-modulation strategies that separately have been employed to treat vascular abnormalities in tumors. Even though these strategies have reached the clinic, their promise has yet to be realized by cancer patients owning to limitations of the methods. My hypothesis is that these strategies can uniquely complement each other and have not only additive, but highly multiplicative synergistic effects on modulating the desmoplastic tumor microenvironment and improving the efficacy of the promising but still of limited use nano-immunotherapy. However, it is crucial that specific guidelines should be developed. To achieve this ground-breaking goal, I will employ a mixture of cutting-edge computational and experimental techniques. I will perform in vivo mice studies in pancreatic cancers and sarcomas to investigate under what conditions these mechano-modulation strategies can be optimally combined to improve treatment efficacy, prevent metastasis and increase survival. In parallel, I will develop new mathematical models to provide useful guidelines for optimizing the experimental protocol. MMSCancer will introduce novel therapeutic strategies for the treatment of drug resistant tumors leading to better therapies.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-STG

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Host institution

KYPRIAKO IDRYMA EREVNON GIA TI MYIKI DISTROFIA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 913 562,50
Address
6 IROON AVENUE
2371 AGIOS DOMETIOS
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 913 562,50

Beneficiaries (2)

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