MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
oleh: Matthew J. Sale, Kathryn Balmanno, Jayeta Saxena, Eiko Ozono, Katarzyna Wojdyla, Rebecca E. McIntyre, Rebecca Gilley, Anna Woroniuk, Karen D. Howarth, Gareth Hughes, Jonathan R. Dry, Mark J. Arends, Pilar Caro, David Oxley, Susan Ashton, David J. Adams, Julio Saez-Rodriguez, Paul D. Smith, Simon J. Cook
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2019-05-01 |
Deskripsi
Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.