ddn Cancer Research News Exclusive: Collaring colorectal cancer
by Kelsey Kaustinen  |  Email the author


NEW YORK—Mount Sinai announced at this year's American Association for Cancer Research 2013 Annual Meeting novel research that could offer a new treatment for colorectal cancer: genistein, a natural supplement from soy.
Genistein is a soy-derived isoflavone, and the National Cancer Institute also identifies it as a phytoestrogen, plant-derived estrogen- like chemicals found in plant foods, and notes that it displays antineoplastic activity and can disrupt signal transduction and induce cell differentiation. Genistein is used commercially as a supplement for menopause and female health issues.
Colorectal cancer's growth is primarily driven by cellular signaling in the Wnt pathway, a network of proteins pivotal to cellular growth. More than 85 percent of colon and rectal cancers display hyperactivity of this signaling pathway. In their work, the scientists—led by Randall Holcombe, M.D., and Sofya Pintova, M.D., both of Mount Sinai—treated colon cancer cell lines with genistein, which blocked hyperactivity of the Wnt pathway and resulted in inhibition of cell growth.  
Their work with genistein was inspired by previous work with natural products, says Holcombe, specifically resveratrol, an antioxidant founds in grapes and red wine and known to play a role in wine's positive reputation in preventing heart disease. Holcombe says they looked at resveratrol's effects on colon cancer prevention, adding that he has conducted research in natural products for some time. Their interest in genistein began as a result of the suggestion that it might affect the Wnt pathway.  
In their research, Holcombe says one of the most interesting discoveries is that genistein reduced proliferation in several types of colon cancer cells, and was equally effective in cell lines with and without the Wnt pathway mutation.
"There seemed to be a correlation between the reduction in growth and the effects on the Wnt pathway, which suggests that the mechanism of action of the genistein at least in part may be through inhibition of the Wnt pathway," explains Holcombe, professor of Medicine in the Division of Hematology and Oncology at the Icahn School of Medicine at Mount Sinai.  
Genistein's potential as a therapeutic isn't confined to colorectal cancers, either. Holcombe notes that several other types of cancer present with activation of the Wnt pathway, including a small subset of breast cancers, sarcomas, some liver cancers and some cancers of the gastrointestinal tract such as stomach cancers. Given its estrogen-like properties, however, he cautions that it wouldn't be recommended for breast cancer.  
"If you look at colon cancer, it's true about 85 percent have activation of this Wnt signaling pathway, and that activation occurs because of a mutation in the cancer cells," says Holcombe. "Genistein appears to work on colon cancer cells, at least from our work in the laboratory, whether these cells have this activating mutation or not, which is a good property … so we think it may be useful for patients with colon cancer as something that may be additive to the effects of other chemotherapy. And in fact, there is some other literature that suggests that genistein may actually be not just additive but also synergistic with certain types of chemotherapy. So we're hopeful that the addition of genistein to a treatment regimen may actually lead to improved response rates for patients with metastatic colon or rectal cancer."
As for whether genistein might have any preventive effects, Holcombe says the answer to that question is "perhaps." It's been tested as a preventative in prostate cancer because of its estrogen-like properties, but the studies "were not definitive," and he adds that determining whether it could play a role in colon cancer prevention will "take some additional study to sort out."  
Natural products such as genistein will most likely continue to play a role in medicine, particularly cancer, according to Holcombe.
"I think that natural products probably in the future will have its greatest role if we can identify where they work for cancer prevention, because they tend to have a very low side effect profile, and so it's something that could be utilized in that setting," he explains. "For cancer treatment, I think the role of natural products will probably be not as an individual therapy for cancer, because I don't think they have enough activity in and of themselves to provide that much benefit, but more as an adjunctive treatment along with other cytotoxic chemotherapies or targeted therapies for cancer."  
The researchers will continue this research by initiating a clinical trial later this year evaluating genistein in combination with chemotherapy for patients with metastatic colon and rectal cancer, says Holcombe. They will also do additional lab work "to look at the potential synergy between genistein and chemotherapy medications," identify which combinations might work well together and then investigate them further.  
"Genistein is a natural product with low toxicity and few side effects, and our research shows that it may be beneficial in treating colorectal cancer," said Holcombe. "This is an exciting area of research and we look forward to studying the benefits of this compound as an adjunctive treatment in colorectal cancer in humans."
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