Researchers have found that disrupting a metabolic process called lipoylation can make cancer cells more vulnerable to certain treatments.
The study shows that the enzyme LIPT1 links cell metabolism to DNA stability. When LIPT1 is blocked, a substance called 2-hydroxyglutarate builds up, causing DNA to become overly compacted. This slows DNA copying and leads to breaks in the genetic material. Cancer cells then rely heavily on the repair protein PARP1 to survive these damage events.
Because of this, tumors with low LIPT1 levels may respond better to PARP inhibitors. Researchers also suggest combining PARP inhibitors with CPI-613, an FDA-designated orphan drug that blocks lipoylation, which showed strong cancer-killing effects in preclinical studies.
The findings suggest metabolism plays a direct role in DNA repair, not just energy production. Scientists now plan to study whether LIPT1 levels can help guide personalized treatment in cancers such as non-small cell lung cancer.