Researchers at NYU Langone Health discovered that resistance to the leukemia drug venetoclax arises due to increased mitophagy, the process by which cancer cells break down and recycle their mitochondria. This finding suggests that inhibiting mitophagy could enhance the drug’s effectiveness. In their study, they noted elevated levels of mitophagy-related genes, particularly Mitofusin-2 (MFN2), in drug-resistant leukemia patient samples compared to non-resistant ones. Combining venetoclax with chloroquine, a known mitophagy inhibitor, was shown to restore its ability to kill cancer cells in mouse models and human samples.
The study’s investigators stress the clinical significance of overcoming venetoclax resistance, especially for acute myeloid leukemia (AML), which has a poor prognosis, with less than a third of patients surviving beyond five years. They propose future clinical trials to explore if the combination of chloroquine and venetoclax can prevent disease recurrence. The research indicates that targeting mitophagy could be a promising strategy for improving leukemia therapies. Currently, treatment options for AML include chemotherapy, targeted therapies, and bone marrow transplants, but resistance to drugs remains a significant challenge.
