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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.
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.
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.
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