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    Stem Cells May Be at Root of Cancer

    New Research May Explain Why So Many Tumor-Fighting Treatments Now Fail

    A New Model for Cancer continued...

    "In this theory, any cell that gets the right series of mutations can become cancer," he says.

    In the stem cell hypothesis, cancer is driven by specific cells that contain stem cell properties, Wicha says. These cells then reproduce and replenish malignant tumors.

    Currently, most treatments target cancer cells, but not necessarily cancer stem cells, he says. While the treatment may shrink the tumor and keep it in check for a while, eventually, the untreated cancer stem cells proliferate into cancer cells, leading to a return of the tumor and death, he says.

    If the treatments targeted the cancer stem cells, however, the tumor would lose the ability to generate new cancer cells, eventually resulting in a cure, Wicha says.

    Think dandelions, says researcher Peter Chu, PhD, of Biogen Idec in San Diego. "If you cut a weed and don't get the root, it will grow back," he tells WebMD. "So if you don't [kill off] cancer stem cells, you're not going to see better long-term survival."

    Wicha notes that the concept that stem cells cause cancer is not new. But recent advances in molecular biology -- such as the development of tests that allow researchers to locate and measure the cancer stem cells -- are giving it new credibility, he says.

    Stem Cells Drive Aggressive Breast Tumors

    Experiments in Wicha's lab show that two genes, PTEN and HER2/neu, that are associated with aggressive breast cancers have stem cell properties. Defects in either gene are tied to faster-growing tumors that are more likely to return.

    The researchers studied three types of genetically altered breast cancer cells: One had the PTEN defect, one had the HER2/neu defect, and one had both genetic alterations.

    Results showed that that either defect increases the stem cell population by two to five times. Furthermore, there was an approximately tenfold increase in the stem cell population when they created a cell line with both PTEN and HER2/neu defects.

    Then, the researchers injected the three types of genetically altered cells into mice. Cells with either defect induced the growth of tumors that were four to six times more aggressive than normal. Injection of the cells with both alterations caused tumors that were 10 times more aggressive.

    Wicha believes the experiments may help explain why Herceptin, the biologic therapy that targets the HER2 protein on cancer cells, works so well.

    "We believe that knocking out the tumor-causing cancer stem cells explains why Herceptin reduces that chance of cancer coming back by 50% [in women with HER2 positive breast cancer], although that remains to be proven," he says.

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