WP4255 - Non-small cell lung cancer - Homo sapiens

Non-small cell lung cancer (NSCLC) represents 85% of lung cancer and is defined as any type of epithelial lung cancer that is NOT small cell carcinoma, including squamous cell (SCC), adeno (AC) and large-cell carcinoma.
Mutations in NSCLC:
KRAS (mutated in ~29% of NSCLC patients) inactivates its GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus.
Mutations or overexpression of EGFR (~22% of NSCLC patients) leads to increased proliferation.
The abnormal fusion of EML4-ALK (~5% of NSCLC patients) leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis.
Inactivating mutation of p53 (~50% of NSCLC patients) leads to reduced apoptosis and proliferation.
The protein encoded by the p16INK4a, CDKN2A, inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. p16INK4a is mutated in ~12% of NSCLC patients, which leads to a loss of this inhibitory effect.

RARB is a nuclear retinoic acid receptor whose function is often lost in NSCLC, leading to a loss of cell growth control.

This pathway was developed based on [KEGG](https://www.kegg.jp/dbget-bin/www_bget?pathway+map05223). Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.