Emerging targets in targeted protein degradation (TPD) in cancers - PDAC, Gastric, MSS-CRC, NSCLC, Urothelial cancers

1. Clinical translation of undruggable protein targetsTPD Platform & Ligase Innovation23 documents (7%)
2. Lack of approved therapies for KRAS G12D mutationsOncogenic Driver Degraders21 documents (6%)
3. Colorectal cancer recurrence from drug tolerant stem cellsCell Cycle & Signaling Modulators14 documents (4%)
4. Chemoresistance driven by non coding RNA micropeptidesTPD Platform & Ligase Innovation12 documents (3%)
5. Acquired resistance to covalent KRAS G12C inhibitorsOncogenic Driver Degraders12 documents (3%)
6. BRD4 protein mediated cell proliferation in bladder cancerEpigenetic & Transcriptional Regulators12 documents (3%)
7. Lack of ligand binding pockets in oncogenic proteinsCell Cycle & Signaling Modulators12 documents (3%)
8. Kinase mediated immune suppression in hematopoietic cellsCell Cycle & Signaling Modulators11 documents (3%)
9. Narrow therapeutic window for systemic protein degradationCell Cycle & Signaling Modulators11 documents (3%)
10. MAPK pathway reactivation despite BRAF inhibitor treatmentOncogenic Driver Degraders10 documents (3%)
11. Poor cell permeability of EGFR C797S PROTAC degradersOncogenic Driver Degraders10 documents (3%)
12. Limited availability of E3 ligase recruitment mechanisms for diverse targetsTPD Platform & Ligase Innovation9 documents (3%)
13. Akt3 mediated osimertinib resistance in lung cancerOncogenic Driver Degraders9 documents (3%)
14. Limited availability of suitable E3 ubiquitin ligase ligandsCell Cycle & Signaling Modulators9 documents (3%)
15. Selective E3 ligase recruitment for pediatric cancersTPD Platform & Ligase Innovation8 documents (2%)

Largest 15 of 51 problems