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)](https://www.phosphosite.org). f51 ea7 e17 c58 b01 f54 cda cda b74 e20 b83 b74 d76 b01 c25 b83 e01 b9a f89 b9a b9a b9a b9a parentid=P06400; parentsymbol=RB1; site=AVIPINGsPRtPRRG; position=ser249; sitegrpid=447975; ptm=p; direction=d parentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=p; direction=u parentid=O15530; parentsymbol=PDPK1; site=skQARANsFVGtAQy; position=ser241; sitegrpid=447693; ptm=p; direction=u parentid=Q92934; parentsymbol=BAD; site=PFrGrsRsAPPNLWA; position=ser99; sitegrpid=447862; ptm=p; direction=d parentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGtRSY; position=ser222; sitegrpid=448513; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGtRSY; position=ser226; sitegrpid=448074; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyr; position=tyr187; sitegrpid=447594; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyr; position=tyr204; sitegrpid=447543; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=EGsFEsRyQQPFEDF; position=tyr1253; sitegrpid=448576; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=EGRNPGFyVEANPMP; position=tyr783; sitegrpid=447667; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=IGtAEPdyGALyEGR; position=tyr771; sitegrpid=448575; ptm=p; direction=u parentid=P31751; parentsymbol=AKT2; site=sDGAtMKtFCGtPEy; position=thr309; sitegrpid=448537; ptm=p; direction=u parentid=P55211; parentsymbol=CASP9; site=kLRRRFssLHFMVEV; position=ser196; sitegrpid=448454; ptm=p; direction=d parentid=O43524; parentsymbol=FOXO3; site=APRRRAVsMDNSNkY; position=ser253; sitegrpid=449108; ptm=p; direction=d parentid=O43524; parentsymbol=FOXO3; site=QsRPRsCtWPLQRPE; position=thr32; sitegrpid=448602; ptm=p; direction=d parentid=P42229; parentsymbol=STAT5A; site=LAkAVDGyVkPQIkQ; position=tyr694; sitegrpid=447767; ptm=p; direction=u c0e b72 d76 c4a cbe c25 38357801 PubMed A plain language summary of the PHAROS study: the combination of encorafenib and binimetinib for people with BRAF V600E-mutant metastatic non-small-cell lung cancer. 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