TOKYO -- Cancer is poorly understood. Researchers are doing their best to change that.
Recent studies show that cancer cells that can adapt to changing environments thrive. These findings are expected to change the way cancer is diagnosed and patients are treated.
Most people who get pancreatic cancer are diagnosed when it is already too late. A group of researchers from Japan and the U.S. in 2013 called the process of a cancer's beginning, growth and metastasis "Darwinian evolution."
"We studied how a tumor grows and spreads, with a focus on gene mutation, and created a model," said Shinichi Yachida of Japan's National Cancer Center, one of the researchers. "It was similar to Darwin's theory of biological evolution."
The model was based on a 2010 paper Yachida published in the journal Nature with colleagues at Johns Hopkins University, where he worked at the time. They removed tumors from deceased pancreatic cancer patients in their pancreas, as well as those that had spread to the lungs, liver and peritoneum. The group then studied how some 20,000 genes changed compared with normal cells.
Survival of the fittest
Cancer occurs when normal cells mutate and damage genes because of factors such as diet, ultraviolet radiation and aging. The researchers hypothesized that they may be able to track the growth of cancer based on gene mutations.
The group found two phenomena in gene changes: those at primary sites, pancreas, as well as at metastatic sites -- other parts of the body to which the cancer spread; and those only at metastatic sites. The primary site group includes such mutations as KRAS and P53. One patient was found to have had more than 30 mutations. In the metastatic sites, the genes undergoing mutations increased most in the peritoneum, followed by the liver and then the lungs.
Mutations are more common farther from the center of tumors, the researchers found. Cancerous cells on the outside of tumors are more similar to mutated cells in other parts of the body.
"Our theory is that cells in the pancreas mutate separately and undergo repeated divisions," said Yachida. "Those cells that have mutated in a way that enables them to thrive even with low levels of oxygen and nutrients survive and proliferate in other organs." This process is similar to Darwin's evolution theory, in which species that adapt to the environment survive.
Scientists have in the past proposed ideas of cancer's evolution. Bert Vogelstein in the 1980s suggested a theory of cancer having a multistage nature. He argued that as cells undergo divisions, damaged ones accumulate and become cancerous in several stages. Ralph Hruban in 2002 proposed a similar theory for the pancreas, but there was no way to test the hypothesis at that time. Advancements in genetic analysis technologies since the mid-2000s enabled the breakthrough. The theories were proved correct by the researchers.
How does understanding cancer's evolution help diagnosis and treatment?
It will lead to the "development of early detection techniques, ways of assessing drug tolerance and predicting chances of recurrence," said Seishi Ogawa of Kyoto University, a kidney cancer expert.
Yachida's group computed the speed of pancreatic cancer growth based on the accumulation of genetic mutations of cells. They found that it takes more than a decade from the time of the first cell mutation to the development of an operable tumor measuring 1-2cm in the pancreas. "If the tumor can be surgically removed during this period, the five-year survival rate will increase about tenfold," Yachida said. The rate currently stands at around 5%.
Imaging technology is inadequate for diagnosis of pancreatic cancer in the majority of patients. Early detection may be possible by checking DNA with a blood test, he added.
One problem with treatment is cancer drug resistance. The ability to precisely determine the specific genetic mutations in cancerous cells would also enable physicians to identify drugs that do not work in particular patients, eliminating the unnecessary administration of medicine, Ogawa said.