cancer stem cells responsible for recurrences

[Lani]

I use the analogy of mold/mildew--they use dandelions!

Cancer Stem Cells Linked to Disease Recurrence

Allison Gandey
February 26, 2007 — Current anticancer therapies may produce dramatic responses, researchers say, but they are unlikely to result in long-term remissions if rare cancer stem cells are not targeted as well. Reporting at the recent Blood and Marrow Transplantation tandem meetings in Keystone, Colorado, investigators showed that a rare population of undifferentiated and long-lived cells responsible for cancer growth may be associated with disease recurrence.

"It is becoming well recognized to those of us working in the field that many cancers arise from rare self-renewing cells that are biologically distinct from their more numerous differentiated progeny," lead investigator Richard Jones, MD, from the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, told Medscape. "This is something that many treating oncologists may not be fully aware of."

Dr. Jones pointed out that while new therapies that tap into this concept are not yet ready for prime time, differentiating cancer stem cells from the bulk of cells could lead to exciting new treatments. "A paradigm change is needed," he said. Many currently active treatments have been developed to target differentiated cancer cells and may provide little activity against the biologically distinct cancer stem cells.

In a news release about the findings, Dr. Jones compares current cancer treatments to mowing dandelions. "You get rid of the dandelions, but if you don’t destroy the root, the dandelion returns," he says. Like the root, there may be a small minority of cancer cells that are able to divide and grow into new cancer cells.

Clinical Response May Not Translate Into Improvements in Overall Survival

Clinical trials are now under way at Johns Hopkins and other centers to test novel therapies such as monoclonal antibodies that will target stem cells. "First, we treat the cancer itself to relieve the symptoms in patients with techniques such as chemotherapy or stem-cell transplant. These treatments interfere with the process of cancer cell division — that is, they are effective at the dandelion level," he said. "Then we go after the root — or stem cells.” Results of the clinical trials are expected in about a year or two.

At the meeting, Dr. Jones suggested that objective clinical response to treatments often do not translate into substantial improvements in overall survival. There is surprisingly little evidence that disease response is an appropriate surrogate for survival, he argues.

The major advantage of using clinical response as the primary end point of clinical trials is that it is measurable over weeks to months, allowing the stepwise process of drug development to occur more rapidly and efficiently, Dr. Jones explained. In contrast, demonstrating a survival benefit adds significant complexity to clinical trial design, usually requiring the accrual of large patient numbers and long follow-up to provide statistical significance.

He points out that traditional response criteria measure tumor bulk and may not reflect changes in populations of rare cancer stem cells. Dr. Jones added, "Although we have known about the existence of these cells for some time, we are only now starting to learn more about how to identify and target this very small population of cells, which may not be responsive to the same treatments that are able to kill the other, more numerous cancer cells."

Blood and Marrow Transplantation Tandem Meetings.