Discovery Could Help Prevent Cancer Drug Resistance Before It Starts
Cancer cells are quick to develop resistance to anti-tumor drugs. New research by scientists from the University of California, Davis shows how cancers adapt to evade a class of anti-tumor drugs called BET inhibitors and offers hope for more effective therapies.
The researchers showed that when BET inhibitors eliminate their target protein, BRD4, cancer cells compensate by increasing the production of a related protein called BRD2, which takes over BRD4’s epigenetic functions and allows the tumor to survive and grow. The team showed that many different cancers adapt to BET inhibition in this way, including pancreatic, blood, prostate, brain, breast, skin, and lung cancers. The results, published May 2 in Cellular and Molecular Biology Letters, suggest that developing a combination treatment that targets both proteins simultaneously could block resistance before it can take root.
“If cancer cells can compensate in this way, then just targeting BRD4 is not going to be sufficient,” said first author Suyakarn (Sonia) Archasappawat, a Ph.D. candidate in the Graduate Group in Integrative Pathobiology. “Our results suggest that we could improve patient outcomes across multiple cancers by targeting BRD2 in combination with BRD4 inhibition.”