Reprogramming colorectal cancer: international REWIRE-CAN team

Madelon Maurice, researcher at the Center for Molecular Medicine at UMC Utrecht and the Oncode Institute, is one of the seven principal investigators in the international research team REWIRE-CAN. Together with researchers from the United Kingdom and the United States, she has received a prestigious Cancer Grand Challenge (CGC) grant of up to £20 million over approximately five years to develop a radical new approach to colorectal cancer.

Colorectal cancer is the second most common cause of cancer death, and the number of diagnoses is increasing, especially among young adults. “Not all tumors respond well to existing therapies, such as chemotherapy and targeted treatments”, explains Maurice. “This is because cancer cells carefully calibrate their own growth signals: they create an optimal amount of signaling that promotes their growth and survival. Scientists also call this the Goldilocks condition, after the fairy tale of the same name. Not too much, not too little, but just right.”

Hyperactivation

Until now, scientific research has primarily focused on inhibiting these signals, with the idea that blocking growth signals would stop the tumor from growing. Maurice: “That works partially, but a significant proportion of patients develop resistance or don’t respond to treatment at all. Some cancer cells can even enter a kind of hibernation, temporarily ‘evading’ treatment and then becoming active again later.”

The REWIRE-CAN team is therefore opting for a completely different strategy: hyperactivation of signaling pathways. Instead of blocking signals, the researchers will overactivate existing growth signals in cancer cells. This can lead to the cells becoming overloaded and dying, or to them being pushed back to a state where they are sensitive to existing treatments. “Initial results show that cancer cells are often more sensitive to overactivation than healthy cells”, says Maurice. “By controlling the amplification of signaling pathways, we can make the cancer cells treatable again. This is a completely different perspective than what we’re used to in cancer research.”