A team from the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) has been studying the mechanisms behind the metastatic progression of prostate cancer. They've found that a high-fat diet could play a major role in promoting metastasis of what is generally an "indolent" disease.
Indolent cancers are low-risk, slow-growing tumors that can progress so slowly that often no treatment is ever needed. Thyroid, lung and breast cancers can be classified as indolent, as can many cases of prostate cancer. The key thing for a physician trying to plan a treatment after a cancer has been identified is to understand what factors can cause it to metastasize and move to other parts of the body, often with fatal results.
The BIDMC team initially discovered that the absence of two specific genes, PTEN and PML, was linked with the metastatic progression of prostate tumors. But the absence of these two genes in the tumors was not enough to completely drive metastasis, there was still an unknown mechanism at play. It was here the researchers discovered that the metastatic prostate tumors being studied were producing incredible amounts of lipids, or fats. In concert with the absence of the two tumor suppressing genes, it seemed the cells' fat production processes were key to triggering a metastatic progression in the cancer.
"It was as though we'd found the tumors' lipogenic, or fat production, switch," explains Pier Paolo Pandolfi, Director of the Cancer Center and Cancer Research Institute at BIDMC. "The implication is, if there's a switch, maybe there's a drug with which we can block this switch and maybe we can prevent metastasis or even cure metastatic prostate cancer."
Up until now it was difficult modeling metastatic prostate cancer progression in mouse models because the disease simply didn't progress in the animals in ways that were useful for research. But this discovery revealed that simply changing the diet of the animals to mimic the levels of saturated fats found in a human "fast food" style diet resulted in aggressive metastatic progression in the tumors.
The researchers then tested a new drug being developed to tackle obesity called fatostatin. This experimental molecule is being investigated for its ability to decrease the transcription of lipogenic genes in cells. The hypothesis was that the metastatic progression of the prostate cancer could be halted by reducing the tumor cells lipid production and the results were encouraging.
"The obesity drug blocked the lipogenesis fantastically and the tumors regressed and didn't metastasize," Pandolfi says.
The research should have several positive real-world outcomes, including improving the animal models that scientists utilize for metastatic prostate cancer experiments. In terms of helping physicians diagnose whether a prostate cancer is likely to metastasize, this research suggests that if a patient's tumor lacks the key tumor suppressing genes then a potential preventative treatment could be diet, or a future fat-blocking drug.
The research was published in the journal Nature Genetics.
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