Gopal Krishna Ramadas Dhondalay PhD

Project | 25

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Develop predictive biomarkers to advance the clinical translation of novel NF-kappa B targeting agents in Diffuse Large B-Cell Lymphomas (DLBCL)

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NF-κB transcription factors are major drivers of DLBCL etiopathogenesis and malignant cell survival, and yet there are no clinically useful NF-κB inhibitors to treat DLBCL patients. Current inhibitors have severe on-target toxicities of IKK/NF-κB-targeting drugs. Previously the group had targeted a non-redundant cancer-restricted survival module (GADD45β/MKK7) downstream of NF-κB, rather than NF-κB itself. The aims are to develop predictive biomarkers for patient stratification to support the clinical translation of the first-in-class GADD45β/MKK7 inhibitor, DTP3, in the unmet need of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). To achieve these goals, preliminarily we have created a benchmark dataset comprising bulk RRNA-seq, CNV and WES data from previously published studies are integrated and classification of DLBCL subtypes was done using LymphGen model. This project is currently in progress with further plans to improve classification efficiency and predictive marker identification.