A receptor tyrosine kinase driving lung cancer–where dimerization state determines signaling output.
EGFR activation requires ligand binding and receptor dimerization. EGF or other ligands trigger conformational changes enabling homo- or heterodimerization with EGFR, HER2, or HER3. Dimerization activates the intracellular kinase domain, triggering downstream PI3K/AktLoading... and RAS-MAPK cascades.
Oncogenic EGFR mutations (exon 19 deletions, L858R) cause ligand-independent activation, driving proliferation. These mutations predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs).
What EGFR Does: EGFR is a receptor on cell surfaces that receives growth signals. When activated, it triggers cascades (including PI3K/Akt and RAS/MAPK) that tell cells to grow and survive.
In Cancer: EGFR can be overactive due to mutations, amplification, or excessive ligand. This drives uncontrolled growth.
EGFR-mutant NSCLCLoading... is treated with TKIs: first-generation (erlotinib, gefitinib), second-generation (afatinib), and third-generation (osimertinib). Osimertinib is now first-line for EGFR-mutant NSCLC due to CNS penetration and activity against T790M resistance mutations.
Despite initial responses, resistance inevitably develops through secondary mutations (C797S), bypass pathway activation, or histologic transformation. Functional biomarkersLoading... measuring pathway activation could help detect resistance earlier.
Current Drugs: EGFR inhibitors (gefitinib, erlotinib, osimertinib) are standard treatment for EGFR-mutant lung cancer. Antibodies (cetuximab) target EGFR in colorectal and head/neck cancers.
Challenge: Resistance develops. Different mutations respond to different drugs. Treatment selection relies heavily on genetic testing.
EGFR expression by IHCLoading... doesn't predict TKI response–mutation status does. But even among EGFR-mutant patients, responses vary. FRET-based measurement of EGFR dimerization or downstream pathway activation could provide additional predictive information.
This approach has been validated for HER2-HER3Loading... and Akt activationLoading.... The same principles apply to EGFR homo/heterodimers, potentially identifying patients with true pathway dependence.
Beyond Mutation Testing: Genetic alterations tell you what COULD be happening; functional measurement tells you what IS happening.
Connection: EGFR signals through Akt (already validated by QF-Pro). Measuring downstream pathway activation provides functional insight beyond mutation status.
