ReverseTheAdvantage | Reversing the advantage of cancers with Hypoxia and Homologous Recombination Defect (HRD) by using a pan-cancer, composite, lesions-specific biomarker

Summary
Hypoxia-activated prodrugs (HAPs) are a great concept in particular in association therapies more efficient on well-oxygenated cells, such as immunotherapies. CP-506 is a third generation HAP with optimal PK for which we confirmed in more than 20 tumor models that presence of tumor hypoxia is a requisite for prodrug activation. We already had an AI/radiomics-based proprietary IP on a solution to identify hypoxia from standard imaging. Another important determinant for efficacy was the presence of a defective homologous recombination (HRD), a pathway needed to repair the DNA damage of the alkylating warhead of CP-506. A genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD, available open source) is able to detect HRD better as compared to assessing mutation of key genes. It is therefore essential to have a validated software solution integrating both biomarkers. This solution, further developed in this project, will be able to capture intrapatient heterogeneity and make a outcome prediction per patient and per lesion.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101082238
Start date: 01-08-2022
End date: 31-01-2024
Total budget - Public funding: - 150 000,00 Euro
Cordis data

Original description

Hypoxia-activated prodrugs (HAPs) are a great concept in particular in association therapies more efficient on well-oxygenated cells, such as immunotherapies. CP-506 is a third generation HAP with optimal PK for which we confirmed in more than 20 tumor models that presence of tumor hypoxia is a requisite for prodrug activation. We already had an AI/radiomics-based proprietary IP on a solution to identify hypoxia from standard imaging. Another important determinant for efficacy was the presence of a defective homologous recombination (HRD), a pathway needed to repair the DNA damage of the alkylating warhead of CP-506. A genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD, available open source) is able to detect HRD better as compared to assessing mutation of key genes. It is therefore essential to have a validated software solution integrating both biomarkers. This solution, further developed in this project, will be able to capture intrapatient heterogeneity and make a outcome prediction per patient and per lesion.

Status

SIGNED

Call topic

ERC-2022-POC2

Update Date

09-02-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2022-POC2 ERC PROOF OF CONCEPT GRANTS2
HORIZON.1.1.1 Frontier science
ERC-2022-POC2 ERC PROOF OF CONCEPT GRANTS2