A new study suggests that chemotherapy can undermine itself by causing a rogue response in healthy cells, which could explain why people become resistant.
The treatment loses effectiveness for a significant number of patients with secondary cancers.
Writing in Nature Medicine, US experts said chemo causes wound-healing cells around tumors to make a protein that helps the cancer resist treatment.
An UK expert said the next step would be to find a way to block this effect.
Around 90% of patients with solid cancers, such as breast, prostate, lung and colon, that spread – metastatic disease – develop resistance to chemotherapy.
A new study suggests that chemotherapy can undermine itself by causing a rogue response in healthy cells, which could explain why people become resistant
Treatment is usually given at intervals, so that the body is not overwhelmed by its toxicity.
But that allows time for tumor cells to recover and develop resistance.
In this study, by 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.
But chemotherapy causes DNA damage that causes the fibroblasts to produce up to 30 times more of a protein called WNT16B than they should.
The protein fuels cancer cells to grow and invade surrounding tissue – and to resist chemotherapy.
It was already known that the protein was involved in the development of cancers – but not in treatment resistance.
The researchers hope their findings will help find a way to stop this response, and improve the effectiveness of therapy.
Peter Nelson, who led the research, said: “Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA.
“Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies.”
Scientists from the University of Southern California say fasting for short periods may help to combat cancer and boost the effectiveness of treatments.
Their study found fasting slowed the growth and spread of tumors and cured some cancers when it was combined with chemotherapy.
It is hoped that the discovery will prompt the development of more effective treatment plans and further research is now under way.
The study, published in the journal Science Translational Medicine, found that tumor cells responded differently to the stress of fasting compared to normal cells.
Instead of entering a dormant state similar to hibernation, the cells kept growing and dividing, in the end destroying themselves.
Lead researcher Professor Valter Longo, from the University of Southern California said: “The cell is, in fact, committing cellular suicide.
“What we’re seeing is that the cancer cell tries to compensate for the lack of all these things missing in the blood after fasting. It may be trying to replace them, but it can’t.”
Prof. Valter Longo and his team looked at the impact fasting had on breast, urinary tract and ovarian cancers in mice.
Fasting without chemotherapy was shown to slow the growth of breast cancer, melanoma skin cancer, glioma brain cancer and neuroblastoma – a cancer that forms in the nerve tissue.
In every case, combining fasting with chemotherapy made the cancer treatment more effective.
Multiple cycles of fasting combined with chemotherapy cured 20% of those with a highly aggressive form of cancer while 40% with a limited spread of the same cancer were cured.
None of the mice survived if they were treated with chemotherapy alone.
Researchers are already investigating the effects of fasting on human patients, but only a clinical trial lasting several years will confirm if human cancer patients really can benefit from calorie restriction.
However, they highlight that fasting could be dangerous for patients who have already lost a lot of weight or are affected by other risk factors, such as diabetes.
Results of a preliminary clinical trial will be presented at an annual meeting of the American Society of Cancer Oncologists (ASCO) in Chicago this June.
Prof. Valter Longo points out that the study only tests if patients could tolerate short fasts of two days before and one day after chemotherapy.
“We don’t know whether in humans it’s effective,” he said.
“It should be off-limits to patients, but a patient should be able to go to their oncologist and say, <<what about fasting with chemotherapy?>> or without if chemotherapy was not recommended or considered.”
Previous research led by Prof. Valter Longo showed that fasting protected normal cells from the effects of chemotherapy but it did not look at cancer cells.
It is now though fasting may be one way to make tumor cells weaker and more vulnerable.
Prof. Valter Longo added: “A way to beat cancer cells may not be to try to find drugs that kill them specifically but to confuse them by generating extreme environments, such as fasting, that only normal cells can quickly respond to.”
