Antifungal drug eliminates sleeping bowel cancer cells in mice

Researchers at the Cancer Research UK Cambridge Institute have shown in laboratory studies in mice, that itraconazole effectively halts the growth and progression of certain types of bowel cancer. The next step will be to see if this holds true in patients with the disease.

“One of the biggest challenges in treating any cancer is the diversity of different cells within the same tumor. We’ve targeted a type of cell that lies asleep within bowel tumors, remaining unresponsive to treatment and putting the patient at risk of their cancer coming back,” said Simon Buczacki, PhD, co-lead author and Cancer Research UK clinician scientist.

The Cambridge team characterized the molecular nature of dormant bowel cancer cells. These “sleeping” cells are resistant to drugs, including chemotherapy, which work by targeting cells that are actively growing. So even if it looks like a treatment has worked, some of these dormant cells can later awaken after treatment has finished and lead to the tumor re-growing.

The scientists identified two key pathways* involved in cell dormancy and used miniature bowel tumors grown from the cells of mice with cancer, to test different drugs targeting these pathways.

They found, for the first time, that itraconazole blocked signals from a pathway called Wnt, which is implicated in the growth and spread of many different cancers. This led to the tumors collapsing in the mice–dormant cells disappeared and the tumor stopped growing.

“What’s interesting is that this drug seems to kick both dormant and non-dormant cells into action,” said Buczacki. “It forces cells back into a short cycle of growth before slamming on an irreversible ‘stop’ button, entering a permanent standstill that’s known as senescence.”

The next stage will be to test this drug in people. The researchers hope to set up a clinical trial where they can test its effect on patients with hard to treat advanced bowel cancer. They also intend to investigate whether this drug could be more effective in combination with other treatments like chemotherapy.

“This innovative study has taken a step toward addressing one of the biggest challenges in cancer research. Tumours are made up of many different types of cancer cells, which can evolve separately and respond to treatments differently,” said Professor Greg Hannon, director of the Cancer Research UK Cambridge Institute. “The presence of drug-resistant, dormant tumor cells is a problem in many types of cancer. If we find ways to target these cells in bowel cancer, it might provide insights into tackling the problem of dormant tumor cells more broadly.”

Source: Cancer Research UK