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Weakness in lung cancer stem cells identified by Stanford scientists

Cancer cells are a wily bunch. They tend to accumulate mutations so fast that one tumor can harbor cells that are vastly different from one another. But recently researchers have come to the realization that, in many cases, a single category of cells drives the growth of the tumor. These masterminds are called cancer stem cells and, unfortunately, they are often resistant to conventional treatments such as radiation and chemotherapy. Identifying and targeting their weak points is crucial to developing therapies that truly eradicate, rather than simply slow down, cancers.

Yesterday, Stanford pediatric oncologist Alejandro Sweet-Cordero, MD, published a study (subscription required) in Cancer Cell describing a population of cells in non-small-cell lung cancer that display a certain marker on their surfaces called Notch3. Transplanting just these cells from mice with the condition caused new tumors to grow in another mouse. As Sweet-Cordero explained in an e-mail to me about the research:

One issue we are particularly interested in is to understand whether all cancer cells are equally aggressive or whether small populations of tumor cells have special characteristics that make them more important (and therefore more interesting to study).

What we learned is that a small population of cells in our animal model of non-small-cell lung cancer are much more capable of transplanting tumor from one mouse to another.  These cells carry a molecule on their cell surface called Notch3.  Blocking Notch3 expression greatly reduced the ability of tumors in our  model to transplant from one mouse to the next.

Figuring out what drives cancer cell growth in humans is important to Sweet-Cordero, who also treats children with cancer at Lucile Packard Children's Hospital at Stanford. He and his colleagues, which include collaborators at San Francisco-based Genentech, next looked at samples of tumors obtained from human patients with the condition. As Sweet-Cordero described:

To validate these studies we used human primary tumors obtained from Stanford surgeons.  We were able to show that Notch3 blockade also inhibits tumor growth in human lung cancer. Thus our studies establish that lung cancer does appear to have a small population of tumor cells called"tumor propagating cells" or "cancer stem cells" and that these cells require Notch3 for survival.  Further studies will help us determine whether blocking Notch3 with antibodies or other compounds can help reduce the growth of lung cancer.

Previously: When the journalist becomes the patient, A huge sigh of relief for one lung cancer survivor and Former long-term smoker shares her lung cancer screening journey - part I, II and III

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