The white arrows in these two tumor samples point to a subset of tumor cells that are in a resting state.
The white arrows in these two tumor samples point to a subset of tumor cells that are in a resting state. Nature
Scientists reported new evidence Wednesday that supports a provocative theory about cancer.
Three separate teams of scientists said they had, for the first time, shown that so-called cancer stem cells can be found naturally in brain tumors and early forms of skin and colon cancer.
Evidence has been mounting in recent years for the existence of these cells, which would be especially insidious. They are believed to resist standard chemotherapy and radiation and fuel the growth of tumors and relapses.
"After a tumor is treated by many conventional forms of therapy, the non-stem cells in a cancer are wiped out but the cancer stem cells may survive and thereafter regenerate an entirely new tumor, leading to what one calls clinical relapse," said Robert Weinberg, a cancer biologist at the Whitehead Institute for Biomedical Research in Boston.
The existence of these cells has been highly controversial. The evidence came mostly from manipulating cancer cells in laboratory dishes and transplanting human cancer cells into animals. It remained far from clear whether they really occurred on their own and for all types of cancers.
The new experiments set out to answer some of those doubts by studying cancers that occur naturally in laboratory mice.
"This was the first example of examination of a spontaneously growing tumor in its normal site of development where we were able to trace the existence of cancer stem cells," said Luis Parada, a professor of developmental biology at the University of Texas Southwestern Medical Center.
Parada and his colleagues performed a series of experiments in which they used sophisticated genetic techniques to trace and analyze brain tumor cells in mice. Two other teams in Europe conducted similar tests, but this time with early forms of either skin cancer or colon cancer.
All the research is being published this week in three papers in the journals Nature and Science.
"With these three studies we can say that in fact three different kinds of tumors adhere to the cancer stem cell hypothesis," Parada said.
Even though the studies were done in mice, Weinberg, Parada and others say there's no reason to think the findings don't apply to people. And if that's the case, the research could lead to new ways to fight cancer.
"It means that we've identified the enemy, finally," he said.
The key to defeating this enemy may be new drugs that specifically target these cancer stem cells.
"Previously we thought all we needed to do was kill off all the cells in the tumor without having any recognition of the existence of these subpopulations of cancer stem cells," Weinberg said. "Now we come to realize that both the non-stem cells and the stem cells need to be eliminated in a tumor in order for one to have a durable clinical response, which may eventually lead actually to a cure."
But not everyone is convinced. Some scientists remain skeptical that what the researchers have found are really cancer stem cells, or that they exist for all forms of cancer.
"The main issue is, 'Can you prove that these things exist? And that means considering the range of alternative explanations and disproving each one — one after another. And that's just not being done," said Scott Kern, who studies the genetics of cancer at Johns Hopkins. "I think the field has not matured."
Despite the skeptics, drug companies have already started designing drugs to target cancer stem cells.
"These three studies add further impetus to us moving ahead with these trials to try to eliminate these cancer stem cells in the hope that it will improve the outcome for patients with a variety of different kinds of cancer," said Max Wicha, who is studying some of the experimental medicines at the University of Michigan.