USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers - PubMed
6 hours ago
- #TKI resistance
- #Ferroptosis
- #GPX4
- USP20 is identified as a key driver of resistance to tyrosine kinase inhibitors (TKIs) like sunitinib and sorafenib in cancers such as renal cell carcinoma (RCC) and lung cancer (LC).
- USP20 deubiquitinates and stabilizes GPX4, a ferroptosis suppressor, enabling cancer cells to evade ferroptosis and resist TKI treatment.
- Clinical data show co-overexpression of USP20 and GPX4 in RCC and LC patients, correlating with poor prognosis.
- Genetic ablation or pharmacological inhibition of USP20 sensitizes resistant tumors to TKIs by promoting ferroptosis, offering a new therapeutic strategy.
- The study highlights the USP20-GPX4 axis as a targetable mechanism to overcome TKI resistance in cancer therapy.