[suzierose]

Cancer Stem Cell Model (CSC)..new perspectives

by suzierose on Sun Mar 11, 2012 10:17 pm

"A consensus panel convened by the American Association of Cancer Research has defined a CSC as "a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor."12 It should be noted that this definition does not indicate the source of these cells—these tumor-forming cells could hypothetically originate from stem, progenitor, or differentiated cells.13 As such, the terms "tumor-initiating cell" or "cancer-initiating cell" are sometimes used instead of "cancer stem cell" to avoid confusion. Tumors originate from the transformation of normal cells through the accumulation of genetic modifications, but it has not been established unequivocally that stem cells are the origin of all CSCs...snip...Given the similarities between tumor-initiating cells and stem cells, researchers have sought to determine whether CSCs arise from stem cells, progenitor cells, or differentiated cells present in adult tissue. Of course, different malignancies may present different answers to this question. The issue is currently under debate,9,12 and this section will review several theories about the cellular precursors of cancer cells (see Fig. 9.1)."

http://stemcells.nih.gov/info/2006report/2006chapter9.htm



The concern I see here, is that NON -CSC's will be as susceptible to chemotherapy as the cancerous ones.

IOWs:

"most contemporary cancer treatments have limited selectivity — systemic therapies and surgeries remove or damage normal tissue in addition to tumor tissue. These methods must therefore be employed judiciously to limit adverse effects associated with treatment. Moreover, these approaches are often only temporarily effective; cancers that appear to be successfully eliminated immediately following treatment may recur at a later time and often do so at a new site. Agents that target molecules implicated in cancer pathways have illustrated the power of a selective approach, and many researchers and drug developers are shifting toward this paradigm. If the CSC hypothesis proves to be correct, then a strategy designed to target CSCs selectively could potentially stop the "seeds" of the tumor before they have a chance to germinate and spread.

The CSC hypothesis accounts for observed patterns of cancer recurrence and metastasis following an apparently successful therapeutic intervention. In clinical practice, however, some cancers prove quite aggressive, resisting chemotherapy or radiation even when administered at relatively early stages of tumor progression. These tumors therefore have an increased likelihood of metastasizing, confounding further treatment strategies while compromising the cancer patient's quality of life. The presence of CSC in some malignancies may account for some of these metastases. So why do some tumors succumb to therapy, while others resist it? Some scientists have suggested that the tumor aggressiveness may correlate with the proportion of CSCs within a corresponding tumor.40–42 In this scenario, less aggressive cancers contain fewer CSCs and a greater proportion of therapy-sensitive non-CSCs.9"

http://www.oncologystat.com/journals/review_articles/LANONC/The_Developing_Cancer_Stem-Cell_Model_Clinical_Challenges_and_Opportunities.html


This suggests what we are talking about with the resistance to lenalidomide and pomalidomide, where we have a reduced number of cells that are still susceptible but that the stable population is no longer susceptible to therapy, consequently therapy in relapsed/refractory is not very robust.

Most importantly it tells me that QOL is pivotal when selecting therapy, as eradication/cure is highly elusive.