# Autophagy

Source: https://onco.cc/pathways/autophagy/  
OnCo record `autophagy` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- 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.
- 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)

## Notes

- Leading programmes: Amaravadi (Penn) on autophagy inhibition trials; Kimmelman (NYU) on PDAC autophagy and MHC-I; Der (UNC) on KRAS/autophagy.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Autophagy
- Yamamoto et al., Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I (Nature 2020): https://doi.org/10.1038/s41586-020-2229-5

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [KRAS](https://onco.cc/targets/kras/), [PRKAA2](https://onco.cc/targets/prkaa2/)
- institutions: [Abramson Cancer Center, University of Pennsylvania](https://onco.cc/institutions/penn-abramson/), [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- key papers: [Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I](https://onco.cc/key-papers/paper-yamamoto-nature/)
- terms: [Hallmark: resisting cell death](https://onco.cc/terms/resisting-cell-death/)

---
JSON: https://onco.cc/api/v1/entities/autophagy.json