COMBAT-RES
Financiado
Predicting potent drug combinations by exploiting monotherapy resistance
Personalising treatments based on tumour genetic profiles enables cancer precision medicine. However, treating cancers using targeted therapies often fails due to the emergence of drug resistance. Here, my goal is to use drug high...
Personalising treatments based on tumour genetic profiles enables cancer precision medicine. However, treating cancers using targeted therapies often fails due to the emergence of drug resistance. Here, my goal is to use drug high-throughput screens (HTS) combined with computational methods to identify resistance and its biomarkers, and to overcome it with smart drug combinations to empower cancer precision medicine.
Identifying resistance in HTS is challenging: dissecting meaningful drug responses at high concentrations is impossible due to cytotoxicity, making non-responders and resistant cell lines indistinguishable, thus limiting resistance biomarker discovery to frequently mutated cancer genes. To address this, I will employ three approaches: 1) systematically identify non-responding cell lines carrying low-frequency resistance markers; 2) reveal intrinsic resistance driven by gene expression plasticity by conducting my own RNA sequencing experiments and modelling the maximal effect at high drug concentration; 3) identify drugs which increase cell viability, combined with drugs targeting fast proliferating cells. My paradigm shift, that resistance biomarkers become synergy markers, empowers smart drug combinations.
Additionally, I aim to predict drug synergy based on multi-task deep learning using molecular characterisation, QSAR modelling and monotherapies; and, to boost biomarker discovery by identifying clinically-relevant cancer subtypes based on transfer and reinforcement learning.
COMBAT-RES will benefit from data access to a phase III clinical trial in colorectal cancer (COREAD) and access to the largest human pancreas adenocarcinoma (PAAD) combination HTS (currently unpublished) accelerating the delivery of medicine for COREAD and PAAD patients. COMBAT-RES will interrogate the underpinnings of drug resistance, clinically-relevant subtypes and overcome it with highly synergistic drug combinations, enabling the next generation of precision medicine.
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Duración del proyecto: 61 meses
Fecha Inicio: 2020-11-17
Fecha Fin: 2025-12-31
Fecha Fin: 2025-12-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-11-17
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-STG:
ERC STARTING GRANTS
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUN...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
295.73K€ |
Participante