A Tyrosine Kinase Protein Interaction Map Reveals Targetable EGFR Network Oncogenesis in Lung Cancer

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A systematic AP‑MS survey of 90 tyrosine kinases in HEK293 cells (about 400+ AP‑MS experiments) yields a scored interaction map (CompPASS cutoff ~2.5) that uncovers unexpected links to nuclear and lysosomal complexes, validates receptor nuclear localization (DDR1, EPHB6) and a FLT3–PTENB–CDK9 functional axis, and produces a 27‑gene EGFR network score. That score flags 95% of canonical EGFR mutants, about 20% of EGFR wild‑type tumors, predicts erlotinib/dacomitinib sensitivity in PDXs and cell lines, and suggests co‑occurrence with weak drivers (NF1, KRAS G12A, BRAF class‑3), implying up to ~16% of lung cancers reuse EGFR.

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1. 0:00Intro
2. 0:31Complexity and diversity of receptor tyrosine kinases
3. 3:50Hyperactivity of wild type tyrosine kinases in cancers
4. 4:37Systematic tagging and purification of the human tyrosine kinome
5. 8:07Association of protein complexes with tyrosine kinases
6. 9:09Alternate lives of RTKs
7. 12:02Oncogene targeted therapies in non-small cell lung cancer
8. 15:26Modulation of interactors modify oncogene dependence in cancers
9. 16:04EGFR network state in lung adenocarcinoma
10. 20:08EGFR network activity predicts targeted therapy response across 25 lung PDX models
11. 22:14Including network information improves the robustness of prediction in orthogonal models
12. 27:17A new model for oncogenesis explains cooperative driver events for 16% of lung cancers