Inhibition of Autophagy in Cancer Lines

There is an unmet need for selective and specific autophagy inhibitors in cancer research and cancer drug development. Many cancer types rely on autophagy, whereby the cell degrades unnecessary or damaged cellular components, to maintain homeostasis of the cell, particularly in the hypoxic environment of rapidly proliferating tumors. Autophagy pathways have come under increasing scrutiny and numerous proteins have been identified. One such autophagocytic protein is LC3-II, part of the LC3/Atg3 autophagocytic pathway. As an indicator of its significance in the growth of cancer cells, LC3-II is used as a biomarker for prediction of cancer outcomes in patients. Interestingly, while studying the malaria parasite Plasmodium falciparum , we recently demonstrated a rate-limiting step in the LC3/Atg3 pathway, suggesting an Achilles heel for this autophagy pathway. Conceptually, therefore, targeting this step could have profound consequences for any disease process, including cancer. Small molecule inhibitors targeting a protein-protein interaction in the human autophagy pathway result in chemosensation of cancer cell lines as well as induction of apoptosis markers upon drug treatment.

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