Disruption of the pro-oncogenic c-RAF–PDE8A complex represents a differentiated approach to treating KRAS–c-RAF dependent PDAC
Published: 26 April 2024
New article from Professor George Baillie and Dr Connor Blair
Disruption of the pro-oncogenic c-RAF–PDE8A complex represents a differentiated approach to treating KRAS–c-RAF dependent PDAC
Sean F. Cooke, Thomas A. Wright, Yuan Yan Sin, Jiayue Ling, Elka Kyurkchieva, Nattaporn Phanthaphol, Thomas Mcskimming, Katharine Herbert, Selma Rebus, Andrew V. Biankin, David K. Chang, George S. Baillie & Connor M. Blair
link to paper
Allosteric c-RAF Inhibition halts cancer:
- Proliferation, Migration & Adhesion
- Targeting Tumour Growth & Metastasis
Summary
Our research (published in Scientific Reports [link]) highlights, for the first time, a pro-oncogenic role for the c-RAF – PDE8A protein-protein interaction (PPI) in KRAS – c-RAF driven cancer. Targeted disruption of this PPI with a novel cell-penetrating disruptor peptide (DRx-170) therapeutically exploits cross-talk between c-RAF and cAMP/PKA signalling axes, suppressing pancreatic cancer cell proliferation, migration and adhesion. Resultingly, DRx-170 offers a differentiated approach to targeted c-RAF activity and treating KRAS – c-RAF driven cancer, including KRAS mutant pancreatic cancer, colorectal cancer and lung cancer.
Lead optimisation and pre-clinical development of next-generation c-RAF – PDE8A disruptor peptides is on-going. Successful pre-clinical development will enable clinical phase investigation(s), where we hope this novel therapy can make a positive and significant impact in RAS mutant cancer patients with the highest unmet needs.
First published: 26 April 2024
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