project-idea

RB1-Loss Drug Repurposing Navigator for DLBCL

GAK inhibition is tumor-selective in RB1-deficient DLBCL, and OTS167 — already in human trials for solid tumors — potently hits GAK. This opens a rapid repurposing path gated on a single biomarker.

Build a web tool that maps approved and late-stage investigational drugs to their off-target kinase activity profiles, specifically surfacing candidates with potent GAK inhibition. The tool would let researchers and oncologists query 'what drugs already in trials could hit GAK?' and cross-reference those candidates with RB1 status data from DLBCL patient cohorts (e.g., from TCGA or cBioPortal).

The core of the project would be a curated kinase-inhibitor selectivity database (sources: DiscoverX/KINOMEscan, ChEMBL, published kinome screens) filtered to highlight GAK affinity. A secondary layer would pull RB1 loss frequency data by cancer subtype to rank which cancers are most likely to carry the GAK dependency.

The end output could be a ranked shortlist of repurposing candidates with links to existing trial data, preclinical evidence, and RB1 co-occurrence statistics — a one-stop resource for any oncologist or drug developer who wants to act on this finding without starting from scratch.

Who Is This For?

Oncology researchers, translational scientists, and pharma drug repurposing teams who want to act on kinase inhibitor off-target profiles.

Skills & Tools Needed

Python or R for data integration (ChEMBL, cBioPortal, DiscoverX APIs)
Knowledge of kinase selectivity profiling data formats
Basic web frontend (React or Streamlit) for query interface
Familiarity with cancer genomics databases (TCGA, cBioPortal)
Understanding of oncology clinical trial registries (ClinicalTrials.gov API)

Feasibility

medium — Data sources are publicly available but integration requires domain knowledge of kinase pharmacology and cancer genomics; a functional prototype could be built in weeks.

Inspired by: The cyclin-G associated kinase (GAK) is a novel mitotic kinase and therapeutic target in diffuse large B-cell lymphoma

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