gefitinib, erlotinib Cancer Research Results

Gefitinib — Oral small-molecule targeted anticancer drug and first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Gefitinib reversibly competes with ATP for binding to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting EGFR autophosphorylation and downstream signaling pathways involved in tumor-cell proliferation, survival, migration, and resistance to apoptosis.

Drug class: Targeted anticancer therapy; first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI). Gefitinib is an antineoplastic drug but is not conventional cytotoxic chemotherapy.

Primary cancer relevance: Strong. Gefitinib is used particularly for non-small-cell lung cancer (NSCLC) containing sensitizing EGFR mutations, especially EGFR exon 19 deletions and the exon 21 L858R mutation. Tumors containing activating EGFR mutations are generally substantially more sensitive to EGFR-TKI therapy than tumors with wild-type EGFR.

Primary mechanism: EGFR tyrosine kinase inhibition → EGFR phosphorylation ↓ → RAS/RAF/MEK/ERK signaling ↓ and PI3K/AKT/mTOR signaling ↓ → proliferation ↓, cell-cycle progression ↓, survival signaling ↓, and apoptosis ↑.

Typical target/pathway effects: EGFR activity ↓; phosphorylated EGFR ↓; ERK1/2 phosphorylation ↓; PI3K/AKT signaling ↓; AKT phosphorylation ↓; Cyclin D1 ↓; proliferation ↓; cell-cycle arrest ↑; BIM/BCL2L11 ↑; caspase-3/7 activation ↑; apoptosis ↑.

Resistance: Acquired resistance is common. Resistance mechanisms can include secondary EGFR mutations, activation of bypass signaling pathways, phenotypic transformation, and other mechanisms that restore downstream proliferative or survival signaling despite EGFR inhibition.

Typical clinical dose: Gefitinib has commonly been administered orally at 250 mg once daily in approved NSCLC indications.

Alzheimer’s disease relevance: No established clinical therapeutic role in Alzheimer’s disease. Any neurological pathway findings should be considered experimental rather than an indication for clinical use.

Gefitinib; common research designation: ZD1839; trade name: Iressa.

Recommended product classification: Drug — Targeted Therapy / EGFR Tyrosine Kinase Inhibitor.