{"entity":{"id":"autophagy","kind":"pathway","name":"Autophagy","aka":[],"tldr":"Autophagy is the cell's recycling programme. Cancer cells, especially pancreatic and RAS-driven tumours, use it to survive starvation and drug stress, which is why hydroxychloroquine, an old malaria drug that blocks it, keeps appearing in trials.","summary":"Macroautophagy engulfs organelles and proteins into autophagosomes for lysosomal degradation, supplying amino acids and nucleotides under stress. RAS-mutant and pancreatic cancers are autophagy-addicted; KRAS or MEK inhibition further increases autophagy, so hydroxychloroquine or ULK1 inhibitors are combined with trametinib (phase 1/2, PDAC) and with KRAS inhibitors. Autophagy also degrades MHC-I in PDAC (immune evasion) and is context-dependent: tumour-suppressive early, pro-survival late. No selective autophagy drug is approved; hydroxychloroquine achieves inconsistent lysosomal inhibition at tolerated doses.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Autophagy","links":[{"label":"Yamamoto et al., Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I (Nature 2020)","url":"https://doi.org/10.1038/s41586-020-2229-5"}],"tags":["mechanism"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["penn-abramson","cold-spring-harbor"],"pathways":["ras-mapk","pi3k-akt-mtor","cancer-metabolism","antigen-presentation-immunoediting"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yamamoto-nature"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Amaravadi (Penn) on autophagy inhibition trials; Kimmelman (NYU) on PDAC autophagy and MHC-I; Der (UNC) on KRAS/autophagy."],"analogy":"A besieged city that starts recycling furniture into firewood. It keeps the lights on through the siege, and burning the 'wanted posters' (MHC) hides its criminals too.","nodes":[{"id":"stress","label":"Nutrient stress, KRAS/MEK inhibition","x":15,"y":30,"targetId":"kras"},{"id":"ulk","label":"ULK1 / AMPK","x":40,"y":30},{"id":"mtor","label":"mTORC1 (inhibits)","x":40,"y":70},{"id":"phag","label":"Autophagosome","x":65,"y":30},{"id":"lys","label":"Lysosome (HCQ blocks)","x":85,"y":30},{"id":"fuel","label":"Recycled fuel → survival","x":85,"y":70},{"id":"mhc","label":"MHC-I degradation (PDAC)","x":65,"y":90}],"edges":[{"from":"stress","to":"ulk","type":"activates"},{"from":"mtor","to":"ulk","type":"inhibits"},{"from":"ulk","to":"phag","type":"activates"},{"from":"phag","to":"lys","type":"activates"},{"from":"lys","to":"fuel","type":"activates"},{"from":"lys","to":"mhc","type":"activates"}],"interventions":["Hydroxychloroquine + MEK inhibitor or + KRAS inhibitor in PDAC (phase 1/2)","ULK1 inhibitors (DCC-3116) in RAS-driven cancers","Autophagy inhibition to restore MHC-I and immunotherapy response (preclinical)"]},"route":"/pathways/autophagy/","neighbours":{"cancer":[{"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/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"prkaa2","kind":"target","name":"PRKAA2","route":"/targets/prkaa2/"}],"institution":[{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","route":"/institutions/penn-abramson/"},{"id":"cold-spring-harbor","kind":"institution","name":"Cold Spring Harbor Laboratory","route":"/institutions/cold-spring-harbor/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"cancer-metabolism","kind":"pathway","name":"Cancer metabolism","route":"/pathways/cancer-metabolism/"},{"id":"drug-tolerant-persisters","kind":"pathway","name":"Drug-tolerant persister cells","route":"/pathways/drug-tolerant-persisters/"},{"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/"}],"paper":[{"id":"paper-yamamoto-nature","kind":"paper","name":"Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I","route":"/key-papers/paper-yamamoto-nature/"}],"term":[{"id":"resisting-cell-death","kind":"term","name":"Hallmark: resisting cell death","route":"/terms/resisting-cell-death/"}]}}