Novel GIST Therapies
Financiado
Targeted Protein Degradation as a Therapeutic Strategy for the Treatment of Gast...
Targeted Protein Degradation as a Therapeutic Strategy for the Treatment of Gastrointestinal Stromal Tumour GIST
Gastrointestinal stromal tumour (GIST) is the most common subtype of sarcoma in humans and its initiation and progression is predominantly driven by constitutively activating mutations in the receptor tyrosine kinase (RTK) KIT. Th...
Gastrointestinal stromal tumour (GIST) is the most common subtype of sarcoma in humans and its initiation and progression is predominantly driven by constitutively activating mutations in the receptor tyrosine kinase (RTK) KIT. This dependency on KIT led to the approval of kinase inhibitors for the treatment of GIST. Inhibition of KIT activity is effective at treating GIST in the short-term however, the majority of patients eventually develop resistance. This resistance is predominantly due to the emergence of additional KIT mutations. Therefore, the development of alternative KIT targeting therapies, beyond the current state-of-the-art, is paramount for the effective treatment of GIST in the long-term. One such strategy is targeted protein degradation (TPD). TPD is based on drugs called degraders which are compounds that induce the proximity between a protein of interest (POI) and components of the cellular proteolytic machinery resulting in the destruction of the former. Degradation of KIT offers several benefits over inhibition, that may combat resistance in GIST. Firstly, small molecule inhibitors rely on a strong affinity for the POI to be effective whereas degraders can maintain activity when the affinity for the target is compromised by mutations. Secondly, inhibition of protein function is not a requirement for degrader activity and therefore additional ligandable sites on the POI.
In this project, I will employ a multifaceted drug discovery approach with the overarching aim of designing, identifying, and optimising degraders of KIT and investigate their effectiveness in GIST models. In order to explore the full potential of TPD in the treatment of GIST, I will pursue two different modalities of degraders: (i) bivalent (Objective 1) and (ii) monovalent (Objective 2). With a clear clinical translational goal in mind, the optimised degraders will be evaluated in various preclinical models of GIST (cellular and organoid) (Objective 3).
ver más
Duración del proyecto: 34 meses
Fecha Inicio: 2024-04-25
Fecha Fin: 2027-02-28
Fecha Fin: 2027-02-28
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-04-25
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2023-PF-01-01:
MSCA Postdoctoral Fellowships 2023
Cerrada
hace 1 año
Presupuesto
El presupuesto total del proyecto asciende a
165K€
Líder del proyecto
FUNDACIO INSTITUT DE RECERCA BIOMEDICA IRB BA...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
23M
Perfil tecnológico
TRL
4-5
23M