{"entity":{"id":"mrna-translation-eif4f","kind":"pathway","name":"mRNA translation (eIF4F / mTOR)","aka":[],"tldr":"Cancer cells must make protein at furious speed. The eIF4F complex that starts protein synthesis is the funnel where growth signals converge, and drugs that pinch the funnel starve the tumour of the proteins it needs most.","summary":"mTORC1 phosphorylates 4E-BPs, releasing eIF4E to form eIF4F (eIF4E/4G/4A) and translate cap-dependent, oncogene-rich mRNAs (MYC, cyclin D1, BCL-2, MCL-1); MNK kinases phosphorylate eIF4E. Ribosomal protein and rRNA synthesis (POLR1, RNA pol I inhibitors such as CX-5461) are collateral dependencies. Drugs: eIF4A inhibitors (zotatifin, phase 1/2 in ER+ breast and KRAS-mutant cancers), MNK inhibitors (tomivosertib), mTOR inhibitors (everolimus approved), and RNA pol I inhibitors in BRCA/HRD (CX-5461 with PARP). Translation control is a shared node downstream of PI3K, RAS, and MYC.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/EIF4E","links":[{"label":"Fabbri, Chakraborty, Robert & Vagner, The plasticity of mRNA translation during cancer progression and therapy resistance (Nature Reviews Cancer 2021)","url":"https://doi.org/10.1038/s41568-021-00380-y"}],"tags":["mechanism"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["akt","pik3ca"],"drugs":["everolimus"],"companies":[],"institutions":["mgh","mskcc","ucsf"],"pathways":["pi3k-akt-mtor","myc","ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-fabbri-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Sonenberg (McGill); Ruggero (UCSF) on translation control in cancer; Pelletier (McGill) on eIF4A; eFFECTOR Therapeutics."],"analogy":"A factory's single loading dock (eIF4F). No matter how many orders the managers (RAS, PI3K, MYC) shout, everything must pass through the dock. Narrow the dock and the most urgent, oversized orders (oncogene proteins) are the first to fail.","nodes":[{"id":"mtor","label":"mTORC1","x":15,"y":30,"targetId":"akt"},{"id":"4ebp","label":"4E-BP","x":40,"y":30},{"id":"eif4e","label":"eIF4E","x":62,"y":30},{"id":"eif4f","label":"eIF4F (4E/4G/4A)","x":82,"y":30},{"id":"mnk","label":"MNK1/2","x":62,"y":65},{"id":"onc","label":"MYC, cyclin D1, MCL-1 translation","x":82,"y":70},{"id":"ribo","label":"Ribosome biogenesis (Pol I)","x":15,"y":70}],"edges":[{"from":"mtor","to":"4ebp","type":"inhibits"},{"from":"4ebp","to":"eif4e","type":"inhibits"},{"from":"eif4e","to":"eif4f","type":"activates"},{"from":"eif4f","to":"onc","type":"activates"},{"from":"mnk","to":"eif4e","type":"activates"},{"from":"mtor","to":"ribo","type":"activates"},{"from":"ribo","to":"onc","type":"activates"}],"interventions":["mTOR inhibitors (everolimus) approved in breast, RCC, NET","eIF4A inhibitor zotatifin (eFT226) phase 1/2 with fulvestrant/abemaciclib","MNK inhibitors (tomivosertib) in NSCLC (mixed)","RNA Pol I inhibitors (CX-5461, pidnarulex) in HRD cancers"]},"route":"/pathways/mrna-translation-eif4f/","neighbours":{"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"mcl1","kind":"target","name":"MCL1","route":"/targets/mcl1/"},{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"drug":[{"id":"everolimus","kind":"drug","name":"Everolimus","route":"/drugs/everolimus/"}],"institution":[{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"ucsf","kind":"institution","name":"UCSF Helen Diller Family Comprehensive Cancer Center","route":"/institutions/ucsf/"}],"pathway":[{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"paper":[{"id":"paper-fabbri-nat-rev-cancer","kind":"paper","name":"The plasticity of mRNA translation during cancer progression and therapy resistance","route":"/key-papers/paper-fabbri-nat-rev-cancer/"}]}}