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Novel ferroptosis inducers for the treatment of non-small cell lung cancer

Project description

Ferroptosis inhibitors for cancer treatment

Advancements in cancer molecular characterisation have not significantly improved clinical outcomes. Many patients relapse, especially those without identifiable mutations. High PD-L1 expression often leads to disease progression despite treatment. Ferroptosis, a type of cell death, presents a potential treatment avenue. Ferroptosis suppressor protein 1 (FSP1) is crucial in this process and can be targeted to inhibit specific tumours in vivo, making it a promising drug candidate. The ERC-funded FERADICATE project aims to enhance the FSP1 inhibitor family by improving their activity, selectivity, and pharmacokinetics. It will identify a new lead compound that could serve as a preclinical candidate for cancer treatment, advancing FSP1 inhibitors toward clinical development.

Objective

Despite significant advancements in the molecular characterization of certain types of cancer, many of these discoveries have yet to translate into substantial improvements in clinical outcomes. While targeted therapies are available, patients harbouring common oncogenic driver mutations often experience relapse. Prognosis is even poorer for those without identifiable oncogenic driver mutations. In cases with high PDL1 expression, single-agent immunotherapy typically leads to disease progression, whereas patients with low expression levels require additional toxic chemotherapy to achieve comparable outcomes. This underscores an urgent medical need for more effective therapeutic strategies for specific cancer subtypes. Ferroptosis, a form of necrotic cell death marked by the iron-dependent oxidative destruction of cell membranes, offers a pharmacologically tractable avenue for treatment. The strong reliance of certain tumour subtypes on cellular systems to suppress ferroptosis creates exciting opportunities for innovative therapies. We recently identified ferroptosis suppressor protein 1 (FSP1) as the second mainstay in ferroptosis suppression, functioning independently of the main regulator GPX4. Since the genetic or pharmacologic inhibition of FSP1 alone is sufficient to suppress certain tumour types in the in vivo context, FSP1 emerges as a compelling drug target. Here, we aim to further optimize the activity, selectivity, and pharmacokinetic profile of our newly identified FSP1 inhibitor family. We also seek strive to expand our patent portfolio to ensure broad IP coverage. Our primary objective is to identify a new lead compound—or potentially a preclinical candidate—for cancer treatment, thereby advancing FSP1 inhibitors toward preclinical and clinical development. This program has the potential to deliver a substantial value proposition and create opportunities for out-licensing or co-development partnerships.

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

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Call for proposal

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(opens in new window) ERC-2025-POC

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Host institution

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
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
Address
INGOLSTADTER LANDSTRASSE 1
85764 Neuherberg
Germany

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Region
Bayern Oberbayern München, Landkreis
Activity type
Research Organisations
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Total cost

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Beneficiaries (1)

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