Pancreatic cancer is one of the deadliest and most aggressive forms of cancer. Over 250,000 people worldwide will be diagnosed this year and over 95% of them will die from this deadly disease.
The majority of pancreatic tumors display mutations in a gene called Kras. Activation of the Kras protein confers a survival advantage on the cells, signaling them to continue growing, even in the presence of anti-cancer therapies.
Mutations in the Ras pathway are the most common oncogenic events in human cancers and are responsible for an estimated 3 million deaths worldwide. Direct pharmacological inhibition of RAS proteins in the clinic remains challenging.
My recent work revealed three novel approaches to inhibit the Ras pathway in pancreatic cancer.
The first method makes use of a small cell-permeable peptide (WW) to sequester Ras signaling molecules away from the scaffold protein IQGAP1, thus preventing pathway activation.
The second method is based on inhibiting the SMYD3 enzyme, which activates the MEK1/2 kinases in the Ras pathway in cancer cells.
The Third method uses a dual inhibition of BET proteins and HDACs to synergistically suppresses cancer growth and prevent development of resistant tumors.