New research funded by the U.S. National Institutes of Health (NIH) has shattered the prevailing myth that chemotherapy drugs actually fight cancer. To the contrary, researchers from Harvard University and the University of Massachusetts, Amherst, (UMA) have found that these clinical poisons, though sometimes initially effective at stemming the growth and spread of existing tumour cells, eventually induce major stem cell damage that causes even more cancer.
Publishing their findings in the journal Proceedings of the National Academy of Sciences (PNAS), the team that worked on the project investigated how chemotherapeutics affect the body systematically by testing them out on fruit flies. According to an announcement about the study, scientists administered human-equivalent doses of chemotherapy drugs to Drosophila, a type of fruit fly that had been spawned with a human cancer-causing gene, which activated in the flies’ intestinal stem cells.
Fruit flies demonstrate cancer-causing effects of chemotherapy drugs in humans
Drosophila, it turns out, are perfect test subjects for this type of experiment because their micro-environments are aptly suited for evaluating the division, differentiation and death of stem cells as exposed to outside influences. With regard to chemotherapy drugs, Drosophila serve as optimal specimens for extrapolating data on how human stem cells respond to being poisoned with these chemicals.
The team was able to obtain a sample library of 88 currently used chemotherapy drugs from the National Cancer Institute (NCI), as well as a library of 6,000 small molecules from the Harvard Institute of Chemistry and Cellular Biology, which was used to test the drugs. From this, the researchers identified several new compounds, including three Chinese medicinal extracts capable of inhibiting tumours without causing any harmful side effects.
At the same time, at least seven of the chemotherapy drugs tested, each of which is currently in use in Western medicine, were found to cause major side effects, including the over-proliferation of stem cells. Taking these drugs, they learned, causes small “tumour” growths to emerge from the stem cells, which, given the right environment and genetic background, could eventually turn malignant.
“We discovered that several chemotherapeutics that stop fast growing tumours have the opposite effect on stem cells in the same animal, causing them to divide too rapidly,” said Michelle Markstein, a molecular biologist from UMA and co-author of the new study. “This was a surprise, because it showed that the same drug could have opposite actions on cells in the same animal: Suppressing tumour growth on one cell population while initiating growth in another.”
Earlier studies on mice, flies corroborate cancer-causing potential of chemotherapeutics
Related research published prior to this latest study arrived at similar conclusions. The chemotherapy drug doxorubicin was determined in both mice and fly models to induce stem cell overgrowth, specifically by activating certain genetic pathways that resulted in a severe inflammatory response. The end result of this inflammation, in many cases, was cancer.
“We propose that the same side effect may occur in humans based on our finding that it is driven in Drosophila by the evolutionarily conserved Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway,” wrote the authors of the new PNAS study about their conclusions. “An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumour recurrence.”