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Using senolytic agents to suppress the toxicity of chemotherapy

Project description

Reducing chemotherapy side effects with senolytics

Chemotherapy is used to treat cancer, but comes with short- and long-term side effects, including fatigue, organ impairment, and brain damage. Normal tissue treatment-induced senescence is a key cause of these toxicities. With this in mind, the ERC-funded CHEMOPROTECT project aims to test a senolytic cocktail drug that specifically acts on these senescent cells. With transgenic mice that harbour luminescent senescence markers, researchers will measure the cocktail's ability to protect critical organs, such as bone marrow, heart, and muscle, from chemotherapy. If successful, CHEMOPROTECT may not only kill cancer but also reduce the harmful side effects of treatment, resulting in improved patient outcomes and quality of life.

Objective

Many of the clinically used cancer chemotherapies have considerable short-term side effects, including fatigue, bone marrow suppression, nausea, diarrhea, and hair loss. Long-term side effects include cognitive impairment, organ dysfunction, and even secondary cancers. A body of evidence indicates that senescent cells induced by chemotherapy in non-cancerous tissues play a major part in these toxicities of chemotherapy. As part of the SENCAN grant, we have developed a cocktail of two drugs that is efficient in killing senescent cancer cells. This so-called senolytic cocktail synergizes strongly with chemotherapy in eradicating tumors in experimental animals. The senolytic cocktail acts independently of the genetic context of the cancer, thus demonstrating superior efficacy compared to other senolytic agents, which are context-dependent. We will test in this proof-of-concept grant whether this cocktail can also reduce the side effects of cancer chemotherapy by eliminating the senescent cells from non-cancerous tissues in mice. We use transgenic mice that carry a reporter gene that is activated in senescent cells and hence, tissues become luminescent when non-tumor-bearing animals are treated with chemotherapy. In pilot experiments, we have seen suppression of the luminescent signal when mice are treated with our senolytic cocktail post-chemotherapy. In this application, we plan to investigate the effect of the senolytic cocktail on vital organs that are often affected by chemotherapy: the bone marrow, the heart, and muscle (fatigue). If successful, the case for use of the senolytic cocktail in combination with cancer chemotherapy would become even stronger: not only have we already shown that the cocktail synergizes with chemotherapy in eradicating tumors in vivo in SENCAN, but the present work may also support the notion that the senolytic cocktail can suppress the toxicities that are invariably associated with cancer chemotherapy treatment.

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2024-POC

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Host institution

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
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.

€ 150 000,00
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.

No data

Beneficiaries (1)

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