Therapeutic area: Oncology
Disease: Non Small Cell Lung Cancers (NSCLC) / other cancers
Monogenic inroad: Smarca 2
Cellular Model: Patient-derived cell line
Project Origin: DKFZ, Prof. Nicolas Gunkel
Medical need: SMARCA4 mutations have been identified in a high percentage of NSCLCs (up to 30%), and, to a lower extent, in other tumor entities with unmet medical need. SMARCA2 and SMARCA4 are subunits within the chromatin, functioning as an epigenetic regulator that opens and closes chromatin by shifting the positions of histones, helping to turn gene expression on and off. SWI/SNF subunits are frequently found to be mutated in different cancer entities. Several independent synthetic lethality screens identified SMARCA2 as being essential for the growth of tumor cells that harbor loss of function mutations in SMARCA4.
Goal: The project aims for development and implementation of a phenotypic approach exploiting a physiologically highly-relevant disease model and the identification of small molecules targeting SMARCA2 as a tumor driver in SMARCA4-deficient cancers.
Development stage: Hit validation