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dacomitinib + gedatolisib
- Development stage
- Unknown
- Lead developer
- Pfizer
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Dacomitinib is a pan-HER (human epidermal growth factor receptor) tyrosine kinase inhibitor that irreversibly blocks signaling through EGFR, HER2, and HER4. Gedatolisib is a dual inhibitor of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), targeting all class I isoforms of PI3K as well as mTOR. The combination of dacomitinib and gedatolisib has been investigated in preclinical models and clinical trials for various solid tumors, including head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), breast cancer, esophagogastric cancer, and ovarian cancer. The rationale for combining these agents is to simultaneously inhibit two key oncogenic pathways—HER/EGFR signaling via dacomitinib and PI3K/mTOR signaling via gedatolisib—potentially overcoming resistance mechanisms seen with single-agent targeted therapy.
- Other names
- dacomitinib and gedatolisibdacomitinib plus gedatolisib
02
Targets
ERBB4 (Erb-b2 receptor tyrosine kinase 4)EGFR (Epidermal growth factor receptor)PIK3CD (Phosphatidylinositol 3-kinase delta)mTOR (Mammalian target of rapamycin kinase)PIK3CG (Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma)ERBB2 (Erb-b2 receptor tyrosine kinase 2)PIK3CA (Phosphoinositide 3-kinase alpha)PIK3CB (Phosphatidylinositol 3-kinase beta subunit)
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