Chemotherapy can be counterproductive in cancer

US researchers are discovering the counterproductive effects of chemotherapy

08/07/2012

Chemotherapy is considered to be a promising therapy for a wide variety of cancers. In fact, the treatment could potentially accelerate cancer growth in the long term, according to a study by scientists led by Peter Nelson of the Fred Hutchinson Cancer Research Center in Seattle.

As the US researchers report in the journal "Nature Medicine", chemotherapy in cancer can cause a counterproductive effect, as the healthy tissue surrounding the tumor is damaged and stimulated to increase the release of a particular protein. This protein is taken up by cancer cells and helps them survive, Nelson and colleagues report.

Chemotherapy increases resistance and promotes cancer recurrence
Resistance to cytostatic drugs and cytotoxins is by no means uncommon after chemotherapy and a major "barrier to reducing morbidity and mortality due to malignant tumors," the researchers say. The scientists used a so-called genome-wide analysis to examine the response of the cells to the "genotoxic stress induced by cancer therapeutics". They identified a "spectrum of proteins from the tumor microenvironment," which appears to have a significant impact on the resistance of cancer cells and promotes their regrowth after the end of therapy. In particular, the protein WNT16B unfolds here, according to the researchers a fatal effect.

Special protein causes counterproductive effect of chemotherapy
In their study of men with prostate cancer, the scientists investigated why cancer cells in the human organism are comparatively difficult to kill, while the drugs usually have a much clearer effect outside the body. They found that the genotoxic stress of chemotherapy causes genetic alterations (DNA damage) in healthy tissue that lead to increased production of the protein WNT16B. "The expression of WNT16B in the prostate tumor microenvironment dampens the effects of chemotherapy, promotes survival of the tumor cell and the progression of the disease," the US scientists report in the latest article. Thus, the effectiveness of chemotherapy is fundamentally questioned. "It may even be counterproductive," says the research team.

Discovered protein interacts with cancer cells
It is often observed in cancer patients that tumors initially respond well to chemotherapeutic treatment, but then continue to accelerate their growth. The US researchers have now apparently found the reason for this new cancer growth. Nelson explained that the protein WNT16B interacts with the cancer cells, thereby stimulating the cancer cells to grow. At the same time, their resistance to the cytotoxic agents (or cytotoxins) and their ability to survive further chemotherapy increases significantly. The counterproductive effect of chemotherapy found in men with prostate cancer has also been confirmed in comparative studies in women with breast cancer and ovarian cancer.

Future of chemotherapy uncertain
The consequences of the current findings for chemotherapeutic cancer treatment in the future can hardly be estimated. While the US scientists are talking only about a reduction in the dosage of chemotherapy or the concomitant administration of WNT16B antibodies, the question is actually whether chemotherapy in view of the clearly counterproductive effect in its present form even makes any sense. Especially with cancers for which other treatment approaches are available. The prophylactic administration of cytostatic drugs after surgical removal of the tumor generally seems rather critical in view of the new findings. However, if chemotherapy is the only hope of success, patients are unlikely to be interested in a potentially counterproductive effect. (Fp)

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