Below find and article by Nicolas Padron, M.D. and links to several articles on the subject of cancer stem cells.

Though the concept of cancer stem cells is still controversial among oncologists, the idea has been well researched and makes perfect sense when it comes to myeloma.  Most all survivors experience some sort of remission and the cancer always returns.

Evidence for myeloma cancer stem cells: are the myeloma cancer stem cells the root cause of myeloma and will eradicating these cells  lead to the cure for myeloma?
 
 
  Stem cell are the primordial cells of the body that produce or replenish the normal cells of the body.   Cancer stem cells (cscs) are also primordial cells in the body, but these cells produce and replenish cancer cells.   The existence of cancer stem cells has been debated for over a century, going back to at least 1902 when a Scottish biologist named Beard postulated on the existence of germ-cells that can produce malignancy, which he published in the journals,  Lancet, and later JAMA.

    This leads us to the "cancer stem cell hypothesis" which states that cancer stem cells are the root cause of cancer by producing cancer cells and more cancer stem cells.  To cure cancer, these stem cells must be eradicated.  If  these cells are not eliminated, they keep producing cancer cells indefinitely.    Proof of the existence of the csc had been missing until 1994 when U Toronto researchers discovered cscs in AML (leukemia).  Since then, cscs have been discovered in various cancers including myeloma, although many doctors remain skeptical of their existence and/or role in cancer.

   Current cancer treatments, including chemotherapy, radiation, surgery, and stem cell transplants have focused only on killing cancer cells, not the cancer stem cells.   Since these treatments are not effective on the cscs, the cancer can reoccur when the surviving cscs regrow the cancer cells.  One of the enigmas of current cancer treatments is that often patients can go into complete remission, with no evidence of cancer, but the cancer can still reappear (relapse).   This may be because of the cancer stem cells that remain and are not detected by traditional  methods.  So, current cancer treatments can be looked at as killing a weed above ground and leaving the root intact.  The root soon regrows the weed plant.

   The myeloma csc was discovered in 2003 by researchers at Johns Hopkins, but not all doctors have accepted this discovery.  Hopkins researchers were able to find these cscs by markers on their surface that distingish them from myeloma cancer cells.   Specifically, myeloma stem cells had CD 19/20 pos and CD138 neg markers.   Myeloma cells are CD19/20 neg and usually CD 138 pos.    In vitro, only the CD19/20 pos cells grew myeloma cells which were now CD19/20 neg.   They also tranplanted both cell types into research mice and discovered that only the CD19/20 neg cells produced the cancer in the mice.   So they now had a new cell type in myeloma, the stem cell.
  
   The research has continued at Hopkins on the myeloma cscs, including research on various therapeutic agents to combat these cells via apoptosis and differentiation.   Hopkins researchers are currently conducting a trial of rituximab against  myeloma stem cells in patients, and are planning a trial of GRN163L (telomerase inhibitor) against the myeloma csc in patients in late 2007.  Furthermore, these same researchers have conducted preclinical trials of cyclopamine on myeloma cscs in 2006, and may have other agents to study, such as parthenolide, in the near future.  Parthenolide is already known to kill leukemia stem cells (U Michigan). 
 
    Hopkins latest research on myeloma cscs was published online in PNAS, Feb 27,2007, showing that myeloma cscs reside in a stem cell compartment, and that these cells can be eliminated by cyclopamine which causes differentiation of the cancer stem cells so the cells can no longer reproduce themselves or cancer cells.   Weill Medical College of Cornell in New York is planning a trial of PD0332991 aimed at the  "clonogenic" cells of myeloma.

   In summary cancer stem cells have been discovered recently as the root cause of cancer by producing cancer cells.   If myeloma stem cells are indeed the cause of myeloma at the cellular level, then eradicating these cells should produce curative results.    Johns Hopkins researchers believe they have discovered these cells and are advancing their research to find targeted treatment to eliminate these cells.   Although there are many research hospitals that treat myeloma, only Hopkins is focusing on the cancer stem cell in this disease.  
 References available upon request.    Nicolas Padron, M.D.

Study Supports a Stem Cell Origin of Cancer

Researchers at the University of Southern California (USC) recently made significant strides toward settling a decades-old debate centering on the role played by stem cells in cancer development. According to the study’s findings, which appear in an upcoming issue of Nature Genetics and now available online, genes that are reversibly repressed in embryonic stem cells are over-represented among genes that are permanently silenced in cancers; this link lends support to the increasingly discussed theory that cancer is rooted in small populations of stem cells.