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"CANCER" STEM CELLS

What we provide. We analyze molecular, cell biological, xenotransplantation, immunological and tumor pathology data on the properties of cell populations designated in the literature as "cancer" stem cells and their proposed role in underpinning tumour drug resistance. We also evaluate the patent positions relating to the commercial use of such entities.

"Cancer" stem cells. "Cancer" stem cell populations are being actively promoted as the latest targets in the cure for cancer. The claim is that they can be specifically identified and specifically eliminated. If so, then the primary tumour will be shut down, drug resistance will not develop and metastases will not occur. Companies such as GlaxoSmithKline, OncoMed Pharmaceuticals, Arius Research, Raven/VaxGen and Geron have together made billion dollar investments in the cancer stem cell area, but how much of the current marketing stems largely from attaching the word "cancer" to stem cells, rather than from producing relevant clinical data from patients?

The projections on the clinical usefulness of human cancer stem cell populations draw heavily on xenotransplantation data from mice, data which are neither robust nor easily transferable to the individual patient. Critical evaluations of some of these points have been provided in Cancer Research by Professor Scott Kern of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland USA.

To make therapeutic sense of this controversial area, our evaluations focus on primary clinical data on human tumor development. The central issue from the point of view of the oncologist, the patient and Big Pharma is this; does killing cancer stem cells improve patient survival? Second, can drug delivery be sufficiently specific to eliminate just the cancer stem cells without the collateral damage to normal cells that carry the same marker combination? Third, are the cells that are drug resistant (and which repopulate a tumor after chemotherapy), cancer stem cells, or is multidrug resistance a property of the heterogeneity of non-stem cells in a tumour?

Our analyses. We have published our initial evaluations of cancer stem cells in Genetic Engineering and Biotechnology News and the commercial reality is that the cancer stem cell field is particularly opaque from the scientific, clinical and patent perspectives. Some major patent claims are essentially unworkable, with definitions that bog down in the important area of “stemness” and with dubious inferences about cell identity drawn from tumourous growths in immunocompromised mice, as compared to inferences from human embryology and pathology.

Balls of cells that grow in tissue culture dishes and give rise to cells with some properties of ectoderm, mesoderm or endoderm, are far removed from cognate growths in a patient. Similarly, balls of cells that grow in differentially immunocompromised mice where the success of xenotransplantation is dependent upon the genetic background of the mice, their diet, hormonal supplements and the site of transplantation, are also far removed from cognate human growths, especially teratomas (see the interview in WOZ Die Wochenzeitung). Thus xenotransplants, for example, are not models for human saccrococcygeal, retroperitoneal, cervical, intrapericardial and intracranial teratomas, whose distribution in the human body is so informative. The growth disturbances which give rise to the human teratomas largely emanate from the notochord and contiguous structures which are derived by invagination of tissue at Hensens node. Determining what is clinically relevant, involves knowing how to sift the mass of useless information from that which is so precious. This is what we do. 

The way ahead. Secure Genetics evaluates the clinical and commercial opportunities in this cancer stem cell area, particularly as they relate to metastatic cancers and to multidrug drug resistance.

 

 

2007, Kern, S.E & Shibata, D. Cancer Research, 67, 8985-8988. The fuzzy math of solid tumor stem cells: a perspective.

2008, Miklos, G. L. G., Baird, P. J. & Haines, I. E. Genetic Engineering and Biotechnology News, May 1 29, #9, 6-8. Cancer stem cells; fact of fiction?

2008, Engelbrecht, T. interview of George L Gabor Miklos in; WOZ Die Wochenzeitung, 14 August, 33, 23. Moden, Mause, Metastasen.