Abstract
BackgroundCytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin’s disease, high grade lymphomas and some of the rare childhood malignancies.We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies.In this review we will examine the cancer stem cell/cancer cell relationship of each of the chemotherapy curable malignancies and how this relationship impacts on the resultant biology and pro-apoptotic sensitivity of the varying cancer cell types.DiscussionIn contrast to the common epithelial cancers, in each of the chemotherapy curable malignancies there are no conventional hierarchical cancer stem cells. However cells with cancer stem like qualities can arise stochastically from within the general tumour cell population. These stochastic stem cells acquire a degree of resistance to DNA damaging agents but also retain much of the key characteristics of the cancer cells from which they develop. We would argue that the balance between the acquired resistance of the stochastic cancer stem cell and the inherent chemotherapy sensitivity of parent tumour cell determines the overall chemotherapy curability of each diagnosis.SummaryThe cancer stem cells in the chemotherapy curable malignancies appear to have two key biological differences from those of the more common chemotherapy incurable malignancies. The first difference is that the conventional hierarchical pattern of cancer stem cells is absent in each of the chemotherapy curable malignancies.The other key difference, we suggest, is that the stochastic stem cells in the chemotherapy curable malignancies take on a significant aspect of the biological characteristics of their parent cancer cells. This action includes for the chemotherapy curable malignancies the heightened pro-apoptotic sensitivity linked to their respective associated unique genetic events.For the chemotherapy curable malignancies the combination of the relationship of their cancer stem cells combined with the extreme inherent sensitivity to induction of apoptosis from DNA damaging agents plays a key role in determining their overall curability with chemotherapy.
Highlights
Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin’s disease, high grade lymphomas and some of the rare childhood malignancies
Beginning in the 1950s and fully established by the 1980s there has been the development of routine curative chemotherapy treatment for most patients with acute leukemia, high grade non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease, testicular and ovarian germ cell tumors, the gestational trophoblast tumors and for many cases of the rare childhood malignancies [2, 4]
Cancer stem cells in the chemotherapy curable malignancies have proven to be challenging to study but cells with stem like properties have been reported in most of these diagnoses. As discussed below it appears that in each case of the chemotherapy curable malignancies they do not have standard hierarchical cancer stem cell structure, they do have a population of cells that have developed cancer stem cell qualities when arising from the malignant cells themselves in a stochastic or non-hierarchical model
Summary
These biological observations suggests that the chemotherapy curable malignancies share a common theme in that they do not have conventional hierarchical cancer stem cells In each case their cancer stem cells appear to arise either from within the cancer cell pool in the stochastic model, as in ALL, lymphoma and choriocarcinoma, or from a persistent embryonal cell with blocked development as in the childhood malignancies and germ cell tumours. In contrast in the stochastic stem cells arising from CLL, follicular lymphoma and multiple myeloma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
