{"entity":{"id":"shp2","kind":"target","name":"SHP2 (PTPN11)","aka":["SHP-2","PTP2C","SH-PTP2","protein tyrosine phosphatase non-receptor type 11"],"tldr":"SHP2 is an enzyme that sits between growth-factor receptors and RAS and keeps the RAS signal flowing. Blocking it removes the route by which KRAS-driven tumours bounce back from a KRAS inhibitor, which is why SHP2 inhibitors are being paired with KRAS G12C drugs.","summary":"PTPN11 (chromosome 12q24.13) encodes SHP2, a cytoplasmic tyrosine phosphatase that acts downstream of receptor and cytoplasmic tyrosine kinases, positively regulates MAPK signalling and dephosphorylates GAB1, EGFR, ROCK2, CDC73 and other substrates; it is also the effector recruited by phosphorylated PD-1 to dephosphorylate T-cell receptor signalling components (UniProt Q06124). In OnCo, SHP2 is the target of the second-generation allosteric inhibitor sitneprotafib (JAB-3312), combined with the KRAS G12C inhibitor glecirasib in NSCLC, colorectal and pancreatic cancer, and the combination partner named in the garsorasib and glecirasib records.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:9644","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9644"},{"label":"UniProt Q06124","url":"https://www.uniprot.org/uniprotkb/Q06124/entry"},{"label":"NCBI Gene 5781","url":"https://www.ncbi.nlm.nih.gov/gene/5781"}],"tags":["wave5-target"],"related":["glecirasib","garsorasib","kras","octreotide-lanreotide"],"cancers":["nsclc","colorectal","pancreatic"],"sections":[],"technologies":["kras-inhibitors","kinase-inhibitors"],"targets":[],"drugs":["sitneprotafib"],"companies":[],"institutions":[],"pathways":["ras-mapk","rtk-activation","resistance-routes-map","pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"PTPN11","hgnc":"HGNC:9644","ensembl":"ENSG00000179295","uniprot":"Q06124","entrez":"5781","biology":"Because SHP2 relays receptor signals into RAS, inhibiting it blocks the upstream reactivation that limits KRAS inhibitors, and its role in PD-1 signalling gives a second rationale in immunotherapy combinations. Sitneprotafib is described as allosteric, with more potent anti-tumour activity than earlier SHP2 inhibitors.","whereFound":["KRAS G12C-mutant NSCLC and colorectal cancer (combination trials with KRAS inhibitors)","Pancreatic cancer (sitneprotafib trials)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/shp2/","neighbours":{"drug":[{"id":"garsorasib","kind":"drug","name":"Garsorasib","route":"/drugs/garsorasib/"},{"id":"glecirasib","kind":"drug","name":"Glecirasib","route":"/drugs/glecirasib/"},{"id":"sitneprotafib","kind":"drug","name":"Sitneprotafib","route":"/drugs/sitneprotafib/"},{"id":"octreotide-lanreotide","kind":"drug","name":"Somatostatin analogues (octreotide, lanreotide)","route":"/drugs/octreotide-lanreotide/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}]}}