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Rogue Response: Chemotherapy Undermines Itself

A new study, published in Nature Medicine, has suggested that chemotherapy used to treat metastatic cancers can cause a rogue response in healthy cells, which helps to explain why people become resistant to the treatment. Chemotherapy has been shown to lose effectiveness in a large number of patients (approximately 90%) with secondary cancers - those that started out as solid cancers in areas such as the breast, lung, and colon, and metastasised, or spread to a different area of the body. The new research shows that the cause of this resistance could be hidden in fibroblasts - wound-healing cells around tumours discovered to create a protein that may teach the cancerous cells how to evade the treatment.

Researchers at the Fred Hutchinson Cancer Research Center in Seattle looked at the damage chemotherapy was causing to the fibroblast cells surrounding tumours. Because the radiation caused DNA damage, the fibroblasts produced up to 30 times more of a specific protein, Wnt16B, than they should. The protein fuels cancer cells to invade and attack surrounding tissues and evade chemotherapy treatments.

It was already known that Wnt16B was involved in the development of cancers, but not in treatment resistance. The researchers hope they can put a stop to the protein response, and greatly improve the effectiveness of chemotherapy, especially for those patients with multiple cancers. 

Professor Fran Balkwill, a Cancer Research UK expert on the microenvironment around tumours, said: “This work fits with other research showing that cancer treatments don’t just affect cancer cells, but can also target cells in and around tumours. Sometimes this can be good - for instance, chemotherapy can stimulate surrounding, healthy immune cells to attack tumours. But this work confirms that having healthy cells around the tumour can help the tumour become resistant to treatment. 

“The next step is to find ways to target these resistance mechanisms to help make chemotherapy more effective.”

Top image: A human fibroblast cell. Bottom image: Mouse fibroblast cells.

The original paper was published in Nature Medicine. A brief synopsis, and link to the full paper, can be found here.