A team of San Diego scientists say they have discovered how cancer spreads to other parts of the body. The discovery could lead to more effective drugs blocking this process.
The spread of cancer, called metastasis, is a defining characteristic of the disease. Metastasis causes an estimated 90 percent of cancer deaths. It starts when malignant cells activate an embryonic process that creates a kind of cell which can move around the body, according to the study, published Thursday in the journal Cancer Cell.
Understanding this process is essential to stopping it, the study stated. A drug developed from this hypothesis would address a market for targeted cancer therapies estimated to exceed $50 billion by 2015.
The embryonic process starts with epithelial cells, which line external and internal body surfaces, such as the skin and intestines. They are turned into mesenchymal cells, which form connective tissue found in cartilage, skin, muscles and other parts of the body.
This process, called “epithelial-to-mesenchymal transition,” or EMT for short, is essential for embryonic development. But since the genes causing EMT continue to exist in adult cells, they can be reactivated in cancers, which are driven by genetic mutations.
Once the metastatic cells have migrated, they turn off EMT, allowing them to grow in their new location. Cancer cells that don’t turn it off remain dormant, perhaps for years. Keeping these cells dormant could prevent metastasis, the study said.
The study was performed in mice. Its senior author was Jing Yang, an associate professor of pharmacology and pediatrics at University of California San Diego’s School of Medicine. Its first author was Jeff H. Tsai, a postdoctoral researcher in Yang’s lab.
Researchers from the Sanford Burnham Medical Research Institute in La Jolla and the Whitehead Institute for Biomedical Research, in Cambridge, Mass., also participated in the study.
The study’s finding is plausible, and if confirmed in humans, it would greatly change cancer treatment, said Dr. Daniel C. Allison, an assistant professor at Cedars-Sinai Medical Center with expertise in orthopedic oncology.
“This is very exciting. I just want to see how it responds in humans,” Allison said. “But the idea is very good, because the definition of cancer is a cell that grows uncontrollably and then metastasizes. There’s certain tumors that locally can be problems, but if they don’t metastasize, we don’t even call them cancer.”
Allison said targeting EMT, if validated in humans, would cause fewer harmful side effects than chemotherapy drugs. Chemotherapy interferes with cell division, so it mostly kills rapidly dividing cancer cells but also other normal cells that rapidly divide, such as those in hair follicles and the gut. So researchers are looking for specific molecular differences between cancer cells and normal cells to target.
The market for such targeted cancer therapies, as they’re known, is expected to reach $51 billion annually by 2015, according to a 2010 report from Decision Resources. That’s double the 2008 figure of $25 billion.
The EMT-metastasis hypothesis was proposed 10 years ago by French cancer researcher Jean Paul Thiery. Since then, a lot of research has been performed to determine whether the hypothesis is correct.