Obesity is linked to prostate cancer, scientists know, but it’s not been clear-cut why. Last week, however, researchers reported a surprising connection.
When prostate cancers lose a particular gene, they become tiny fat factories, a team at Beth Israel Deaconess Medical Center (BIDMC) in Boston reported in a paper published in Nature Genetics. Then the cancers spread from the prostate, often with deadly effect.
Prostate cancers that have not lost that gene also can spread, or metastasize–in mice, at least–but only if they have a ready source of fat from the diet. That finding suggests that dietary fat can substitute for the loss of the gene, fueling prostate cancer.
Furthermore, the investigators found, an obesity drug that blocks fat production can make metastatic prostate cancers regress in mice and prevent them from spreading.
“What this paper suggests is that fat or high-fat diets promote more aggressive prostate cancer,” said Cory Abate-Shen, interim director of the Herbert Irving Comprehensive Cancer Center at Columbia University, who was not involved with the research.
Now the scientists are planning a clinical trial in men with prostate cancer to see if the obesity drug may be an effective treatment for this cancer.
“That’s really important,” Dr. Abate-Shen said. “Aggressive prostate cancer is lethal, and there are no curative drugs right now.”
The American Cancer Society estimates that prostate cancer will be diagnosed in about 165,000 American men this year, making it the second most common cancer in American men, behind only skin cancer. The tumors often remain in the prostate and do not kill, but when the cancer spreads, it is lethal. About 29,500 men die of prostate cancer each year.
Dr. Pier Paolo Pandolfi, director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess and lead author of the new study, has long tried to study prostate cancer spread in mice, but the rodents were not much help. Few genetic manipulations made prostate cancers spread in the animals as they do in humans.
That conclusion led to the experiment with a new obesity drug, fatostatin. It not only halted the cancer’s spread in the animals, but made it regress. Dr. Pandolfi and his colleagues are now planning a clinical trial with fatostatin to treat prostate cancer in humans. (Ref: The New York Times)
Occasionally, I come across a study where the findings of certain clinical research make me stop, and I mumble something brilliant like: “I didn’t know that. Dammit, they’re on to something.” Here’s my take on why this particular study deserves immediate attention, not just in the medical profession, but among anyone who can read.
For some years now, I’ve been under the mistaken impression that because I’m not obese, I have a lower likelihood of getting prostate cancer. The point is that I thought even if I did, the fact that I’m not obese meant there was a far less likelihood of it spreading and eventually killing me.
Now, this new research demonstrates how it’s the fat contained within the Western diet (not so much in my belly region), in combination with genetic factors, that can cause prostate cancer tumors to spread. This finding has a silver lining in the potential new use of already-available obesity meds, regardless of whether you are in fact obese.Steve's Take: New research demonstrates how it’s the fat contained within the #Westerndiet (not so much in my belly region), in combination with #genetic factors, that can cause #prostatecancer tumors to spread. Click To Tweet
The recent research consists of a set of papers published in the journals Nature Genetics and Nature Communications, says Medical News Today. The first author of the paper published in Nature Genetics is Ming Chen, PhD, a research fellow in the laboratory of senior author Dr. Pier Paolo Pandolfi, who is also the director of the Cancer Center and Cancer Research Institute at BIDMC in Boston.
Researchers at Beth Israel note that prostate tumors tend to be what scientists call “indolent”–so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, the disease is invariably fatal.
“Although it is widely postulated that a Western diet can promote prostate cancer progression, direct evidence supporting a strong association between dietary lipids and prostate cancer has been lacking,” said Dr. Chen.
Epidemiological data link dietary fats (and obesity) to many types of cancer, and rates of cancer deaths from metastatic cancers including prostate cancer are much higher in the US than in nations where lower fat diets are more common.
While prostate cancer affects about 10% of men in Asian nations, that rate climbs to about 40% when they immigrate to the US, mirroring the rates among the native-born US population. That points to an environmental culprit that may work in concert with genetic factors to drive this aggressive, fatal disease.
“The progression of cancer to the metastatic stage represents a pivotal event that influences patient outcomes and the therapeutic options available to patients,” said senior author Pandolfi. “Our data provide a strong genetic foundation for the mechanisms underlying metastatic progression, and we also demonstrated how environmental factors can boost these mechanisms to promote progression from primary to advanced metastatic cancer.”
“It was as though we’d found the tumors’ lipogenic, or fat production, switch,” said Pandolfi. “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,” he added.
Such a drug already exists. Discovered in 2009, a molecule named “fatostatin” is currently being investigated for the treatment of obesity. Pandolfi and colleagues tested the molecule in lab mice.
“The obesity drug blocked the lipogenesis fantastically and the tumors regressed and didn’t metastasize,” said Pandolfi.
In addition to opening the door to new treatment for metastatic prostate cancer, these findings also helped solve a long-standing scientific puzzle. For years, researchers had difficulty modeling metastatic prostate cancer in mice, making it hard to study the disease in the lab. Some speculated that mice simply weren’t a good model for this particular disease. But the lipid production finding raised a question in Pandolfi’s mind.
“I asked, ‘What do our mice eat?’” Pandolfi recalled.
It turned out, the mice ate a vegetable-based chow–essentially a low-fat vegan diet that bore little resemblance to that of the average American male. When Pandolfi and colleagues increased the levels of saturated fats–the kind found in fast food cheeseburgers and fries–in the animals’ diet, the mice developed aggressive, metastatic tumors.
The findings could result in more accurate and predictive mouse models for metastatic prostate cancer, which in turn could accelerate discovery of better therapies for the disease.
Additionally, physicians could soon be able to screen their early-stage prostate cancer patients for those whose tumors lack tumor suppressing genes, putting them at increased risk for progressing to metastatic disease. These patients may be helped by starving these tumors of fat either with the fat-blocking drug or through diet.
Simply put: The Western diet may drive prostate cancer metastasis. This points to a high-fat diet as the main environmental–that is, non-genetic–factor in the spread of prostate cancer. The findings also pave the way for new therapies, explain the researchers, as patients who have metastatic tumors may be helped by depriving these tumors of fat.
This could be done either by using fatostatin or other fat-blocking drugs, or through dietary interventions.
The findings shed new light on the complex interplay between our genes and dietary fat, as well as on the role of this dynamic in promoting the spread, or metastasis, of prostate cancer.
As Dr. Pandolfi says, the results of this research “are tremendously actionable, and they surely will convince you to change your lifestyle.” The studies also “pave the way for the new use of existing drugs in the fight against prostate cancer.”
Okay, Dr. Pandolfi. Point well taken. Just because I’m not fat (yet) doesn’t mean I should be chowing down on the Big Macs, fries or other source of high dietary fat. And not just for the cardio but now also for the prostate issues. (Any people in high US govt. office listening?)