William Matsui, M.D., an assistant professor of oncology and other researchers at the Johns Hopkins Kimmel Cancer Center have discovered that cancer stem cells for multiple myeloma, have many properties similar to normal stem cells, thus making the bone marrow cancer treatment resistant.
This study led by William Matsui has paved way for treatments that overcome the cells' drug resistance.
'Nature made normal stem cells very hearty for a reason, namely to survive and help repair damaged tissues and organs after injury or illness. To us, it makes sense that the same processes that protect normal stem cells also exist in cancer stem cells to make them resistant to chemotherapy. We need to develop new ways to target the specific biology of cancer stem cells to prevent the continued production of mature tumor cells and disease relapse,' said Matsui.
Richard J. Jones, M.D., professor and director of bone marrow transplant at Hopkins' Kimmel Cancer Center, added: 'Cancer stem cells that have distinct biology and drug sensitivity as compared with the bulk of a cancer may explain why multiple myeloma, like many other cancers, so often relapses even after chemotherapy puts patients into remission.'
Though the existence of cancer stem cells is highly debated, some scientists still see it as a useful explanation for the long history of difficulty in overcoming some cancers' persistence.
Earlier, the researchers had discovered a rare stem cell in myeloma, present in less than one percent of all the cancer cells. While working with cell samples from myeloma patients, the researchers found that immune system B-cells give rise to this stem cell which in turn is capable of giving rise to the malignant bone marrow cells characteristic of the disease.
In the current study, stem cells from the blood of four patients with multiple myeloma were isolated and transplanted into mice. As a result, all the mice developed hind-limb paralysis and showed signs of cancer in the bone marrow. On the other hand, plasma cells that were transplanted from multiple myeloma patients to mice did not engraft.
According to the scientists, they can get more evidence of these cells acting as cancer stem cells by recreating the disease in mice.
The response to four different chemotherapy medications commonly used to treat patients with the disease: dexamethasone, lenadilomide, bortezomib and 4-hydroxycyclophosphamide, was compared in case of these special stem cells was compared and the bulk of multiple myeloma plasma cells,
It was found that while all four agents considerably suppressed the growth of the plasma cells, none of them inhibited the stem cells.
Surprisingly, it was noted that the multiple myeloma stem cells resemble other types of adult stem cells and exhibit similar properties that may make them resistant to chemotherapy.
The stem cells were found to contain high levels of enzymes that neutralize toxins, like cancer drugs, and force them out through miniature pumps on their cell surface.
According to the investigators, these drug-fighting enzymes and pumps, also present in normal stem cells, may help cancer stem cells resist treatment.
'Standard cancer therapy is like mowing the weed - it gets rid of the disease transiently but the dandelion always grows back. We need to get rid of the root to cure disease, and therefore need a different type of therapy - mowing won't work,' said Jones.
According to Matsui, it will now be possible to follow the rare myeloma stem cells as a marker to know how well a patient is doing during treatment.
The study is published in the recent issue of the journal Cancer Research.