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CORDIS

Anticancer approach based on the Metabolic Disruption of Cancer Stem Cells with high effectivity across a wide range of solid tumours

Project description

A novel agent targeting cancer stem cell metabolism

Cancer stem cells (CSCs), a class of stem-like tumour cells, are at the root of most tumours and drive their progression, chemoresistance and relapse. Despite their central role in cancer, no clinical agents specifically targeting CSCs exist, making them an important yet unmet therapeutic opportunity. The EIC-funded MEDiCS project is developing a promising ruthenium-based anticancer compound (IGN116) designed to selectively target CSC metabolism. Unlike traditional cytotoxic drugs, IGN116 disrupts oxidative phosphorylation, a key energy pathway used by CSCs, reducing their ability to drive tumour growth while sparing healthy cells. Preclinical models show rapid tumour inhibition and a favourable safety profile. The project will advance IGN116 for the treatment of colorectal cancer and pancreatic cancer, two diseases with high incidence, poor prognosis and strong therapy resistance.

Objective

By combining advanced synthetic chemistry with cancer biology, we have demonstrated the potential of ruthenium complex IGN116 as an effective and tolerable anticancer agent, inhibiting tumour proliferation as early as 1-2 days post treatment in pre-clinical PDX models. Instead of acting as a cytotoxic agent, IGN116 interferes with the key bioenergetic pathway (aerobic oxidative phosphorylation) utilized by Cancer Stem Cells (CSC), drastically effecting their stemness potential whilst keeping other cells essentially unaffected. This mode of action is novel both among organometallic and CSC-targeting drugs, conferring IGN116’s effectivity with unmatched low secondary toxicity. Through its unique mechanism of action, IGN116 provides the opportunity to tackle the specific therapeutic challenges of two particularly concerning cancer types that will be the focus of MEDICS: Therapy resistance in the high incidence CRC (1.9 million new cases and 608,000 deaths/year); and poor prognosis in treatment-refractory PDAC (495,773 cases, 466,003 deaths/year). The current TRL is at 3-4 having demonstrated in vivo efficacy, confirmed mechanism of action, and completed full toxicity pharmacokinetic (PK) studies of the isolated IGN116, both in in-house studies and in external CRO-led validation. In MEDICS, we will further develop IGN116 for CRC and PDAC progressing towards TRL5 through: Development of a scalable manufacturing process amenable to GMP; Advancement towards GLP in-vivo studies; and Creation of a spin-out to take the product development towards commercialization. MEDICS will thus tackle a critical challenge in European healthcare: delivering safe and effective cancer treatments, with the potential of benefitting 43,800 CRC and PDAC patients per year in Europe alone by 2040.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-EIC - HORIZON EIC Grants

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Call for proposal

(opens in new window) HORIZON-EIC-2024-TRANSITION-01

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Coordinator

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Net EU contribution
€ 696 355,00
Address
COLEXIO DE SAN XEROME PRAZA DO OBRADOIRO S/N
15782 Santiago De Compostela
Spain
Region
Noroeste Galicia A Coruña
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Participants (4)