An obesity drug may reduce the risk of metastatic prostate cancer.
A majority of prostate cancers grow slowly, but metastatic disease can be fatal.
In a pair of new studies published by Nature Genetics and Nature Communications, researchers have uncovered information about genetic mechanisms that promote metastasis in mice. These findings indicate that the high-fat Western diet may be a driving factor in the spread of prostate cancer.
“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 first author Ming Chen, PhD.
Numerous studies link dietary fat intake with multiple types of cancer. The study authors said that mortality rates from metastatic disease are higher in the United States compared with countries that consume lower fat diets.
“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 Pier Paolo Pandolfi, PhD, MD. “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.”
The partial loss of the tumor suppressor gene PTEN is prevalent among cases of prostate cancer, with complete loss linked to metastatic disease. However, animal studies suggest that the loss of PTEN may not be the only factor that triggers disease progression.
In the new study, the authors aimed to identify other tumor suppressing genes or pathways that may work in conjunction with PTEN to drive prostate cancer metastasis.
A review of genomic data showed that the PML tumor suppressor gene was present in nonmetastatic disease and missing from one-third of metastatic tumors. Another 20% of metastatic tumors lacked PML and PTEN, according to the study.
When the study authors compared localized tumors that lacked PTEN with metastatic tumors missing both genes, they discovered that metastatic tumors created significant amounts of lipids, according to the study.
In tumors that lacked both genes, lipid production was altered.
“It was as though we’d found the tumors’ lipogenic, or fat production, switch,” Dr Pandolfi said. “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.”
The authors then tested the efficacy of an obesity drug for metastatic disease.
“The obesity drug blocked the lipogenesis fantastically, and the tumors regressed and didn’t metastasize,” Dr Pandolfi said.
The authors noted that changing the mice’s diet from vegetable-based food to food high in saturated fats resulted in more animals developing aggressive tumors. This finding could lead to a more accurate model for prostate cancer and better treatments, according to the study.
The authors also said that these results could help screen patients with early-stage disease for the missing genes and treat them with fat-inhibiting drugs and a healthy diet, according to the study.
“The data are tremendously actionable, and they surely will convince you to change your lifestyle,” Dr Pandolfi said.