A cancer patient pushes his drip stand as he walks down a hospital hallway.
Credits: REUTERS/David Gray
They say the treatment can undermine itself by causing a rogue response in healthy cells, which could explain why people become resistant.
Writing in Nature Medicine, U.S. experts said chemo causes wound-healing cells around tumours to make a protein that helps the cancer resist treatment.
Around 90% of patients with solid cancers, such as breast, prostate, lung and colon, that spread - metastatic disease - develop resistance to chemotherapy, the paper says.
For their study, researchers at the Fred Hutchinson Cancer Research Center in Seattle looked at fibroblast cells, which normally play a critical role in wound healing and the production of collagen, the main component of connective tissue such as tendons.
They noticed chemotherapy causes DNA damage that causes the fibroblasts to produce up to 30 times more of a protein called WNT16B than they should.
The team hopes its findings will help find a way to stop this response, and improve the effectiveness of therapy.
Prof. Fran Balkwill, a UK-based cancer research 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 healthy cells surrounding the tumour can also help the tumour to become resistant to treatment.
"The next step is to find ways to target these resistance mechanisms to help make chemotherapy more effective."