Is Cancer Stem Cell the "Messiah of Cancer Cure"?

Sun, October 18 2009, 12:00 AM
Posted By: Sciclips

The existence of cancer stem cells have started as a hypothesis and followed by enormous number of experimental evidences. Still, a large number of scientists in stem cell areas and other research areas are very skeptical about the existence of cancer stem cells. We can believe the existence of cancer stem cells and its role in cancer from all the reported studies on the isolation/characterization of cancer stem cells in various cancers such as leukemia, breast cancer, ovarian cancer, lung cancer, liver cancer, colon cancer etc from past and ongoing research on cancer stem cell. The PubMed searches on cancer stem cells showed more than 5000 articles as of October 2009 and this data indicates that the first research article on cancer stem was published on 1976 (see the box to see all the PubMEd search results). It is evident that the concept of cancer stem is known to us for more than 23 years. If the scientist would have accepted the existence of cancer stem cells a decade ago, possibly we would have been in a better position in finding a cure for cancer or may be closer to achieve this goal? May be the concept of stem cells were not established at that time?

We speculate that the real benefit of stem cells will not come from in vitro differentiation of embryonic (hES) or induced pluripotent (iPS) stem cell into tissues or organs or the injection of stem cells. Better not to be, because these stem cells may be similar to cancer cells (1) and may carry several genetic mutations (2). We do not know the genetic safety of current in vitro grown cells in stem cell therapy. The genetic make up of in vitro grown or maintained stem cells is not fully understood and it may take years to study this; still it is worth to pursue this and we should. Until that time, we should be very cautious in using hES or iPS cells or these stem cells derived cells or tissues or organs for injecting or transplanting in humans. Even for developing drug screening assays, we may not consider in using these stem cells. Proper understanding of the genetic make up of these stem cells derived cells/tissues/organs is needed before we undertake any large-scale drug discovery assays for making any critical decision based on these screening assays. The proponents of hES or iPS cells based therapy may not agree with us on this. This is understandable. We are not saying that a safe stem cell therapy is not possible or stem cells cannot be used for the successful treatment of Parkinsons disease, spinal injury, diabetes etc. It is possible to use stem cells for the treatment of various diseases; several approaches have been well studied and can be used successfully. Among the current approaches, the most promising ones are the induction of resident stem cells in a tissue or organ by specific drugs and the mobilization of stem cells using mobilizing agents/drugs. By using appropriate drugs that induces proliferation and differentiation of resident stem cells may help to regenerate damaged tissues or organs. Drugs or agents that help mobilization of stem cells to the tissue or organs may be a safe approach. Indeed, we can expect the development of very innovative approaches and technologies in future.

Among all the applications of stem cell research, cancer stem cells may be the most promising area that may help us to find a cure for various cancers; may be for all forms of cancers. If this comes true, this would be the foremost contribution of stem cell research to mankind.

It is very interesting to note that studies on cancer stem cells explain the major huddles or challenges and the failure of current cancer therapy. The existence of cancer stem cells in tumors may explain 1) the failure of radiation or chemotherapy 2) the reoccurrence of cancers 3) spreading of cancer from one organ to another organ. Based on these observations, it is possible that extensive research on cancer stem cells may enable to find drug targets and drugs that can inhibit the tumor growth, which may result in a very successful cancer treatment. The cancer stem cells represent only very few fraction of cancer cells in a tumor. This makes difficult to target only the cancer stem cells. May be the radiation/chemo therapies could enrich cancer stem cells, and then we can target the cancer stem cells specifically? We need to answer several questions. Can we use cancer stem cells as vaccines? Do the cancer stem cells in all tumors are similar? If this is true, any approach using cancer stem cell as target may create a universal drug for all types of cancer?

Does the existence of cancer stem cells can explain the origin of cancers? All the tissues may contain stem cells. Do any environmental or genetic factors trigger normal stem cells to become cancer stem cells? Instead of forming normal tissues or organs, do these cancer stem cells form tumors? The self-renewal capacity and the differentiation ability of cancer stem cells can support the tumor formation. Does tumor forms first or the cancer stem cells come first? In other words, do the cancer stem cells are formed from the tumor or the tumors are formed from cancer stem cells? If the tumors are initially formed from cancer stem cells, we might be able to find methods to prevent tumor formation. Extensive studies should be conducted to understand the role of cancer stem cells in early tumor development in order to achieve this goal. If cancer stem cells are formed from tumor cells or tissues, we may be able to approach this issue differently than our current thinking on tumor development. We may consider in finding the role of stem cells, not the cancer stem cells, in tumor development.

Based on the recent reports on iPS cells (3), it is tempting to speculate that there may be naturally induced pluripotent stem cell formation in our body and this may trigger the cancer formation. It may be hard to accept. It is a known fact that small molecules or the expression of certain proteins can induce the formation of pluripotent stem cells from somatic cells under in vitro conditions. If small molecules can induce the formation of stem cells in vitro, why can't some small molecules induce the formation of iPS from somatic cells in vivo? It is possible that a small molecule can induce the formation of iPS cells from normal tissue or organ, which may later form into cancer stem cells. These small molecules can be a mutagen or can be anything that triggers the formation of iPS cells. Since iPS cells can be similar to cancer cells, these cells can be transformed into cancer stem cells, which in turn forms tumor. Can it be a possibility? Another possibility is that a mutagen transforms normal resident stem cells in a tissue or organ to cancer stem cells, which in turn is differentiated into specific tumors. If tumors are formed from cancer stem cells, we might be able to target this with specific drugs.

On the light of the recent report (3) that the iPS cells is a mixture of pure iPS cells and partially reprogrammed intermediatory cells, does this resembles the concept of tumor hierarchy? According to the concept of tumor hierarchy, tumor consists of heterogeneous population of cells with common mutations, but these cells are phenotypically different. It is worth to develop an assay where we could screen all the compounds that induce the formation of pluripotent stem cells (iPS cells) from various somatic cells. If the tumor formation is through in vivo iPS cell formation, we might be able to identify agents that trigger the formation of pluripotent stem cells from different somatic cells. The same assay can be used for the screening of cancer stem cell formation form resident stem cells. These approaches would help in rational drug discovery for each type of cancers.

The concept of cancer stem cells might explain the origin of tumor formation as well as spreading of tumors. In either situations, cancer stem cells opens up possibilities for finding methods to prevent cancer formation and possibly for finding a universal drug for the successful treatment of various cancers. For these reasons, we may consider cancer stem cells as the Messiah of the century. It is the time for scientists to come out from skepticism about cancer stem cells and put their intellectual efforts in understanding the cancer stem cells, which do exist.

References:

Nature 2009 460, 1085-1086:
http://www.nature.com/nature/journal/v460/n7259/full/4601085a.html
Invest Ophthalmol Vis Sci. 2009 Jul 23. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/19628750?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.
Pubmed_RVDocSum
Nature Biotechnology Published online: 11 October 2009 http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.1580.html

Suggestions on new technologies that can be adopted for cancer stem cell research

	Molecular Proteomics Imaging of Tumor Interfaces by Mass Spectrometry
	Mass spectrometry imaging of proteins will be a very powerful tool for the characterization cancer stem cells. The origin, development and functions of cancers tem cells can be studied using this unique MS imaging tool. Abstract of this article

	Imaging of Lipids in Spinal Cord Using Intermediate Pressure Matrix-Assisted Laser Desorption-Linear Ion Trap/Orbitrap MS
	Mass spectrometry imaging of metabolites can be used for characterizing the role of these small molecules in cancer stem cell function and formation. Abstract of this article

Additional information for Cancer Stem Cell

Cancer stem cells - General (PubMed)

Cancer stem cells - Proteomics/Markers (PubMed)

Cancer stem cells - Epigenetics (PubMed)

Cancer stem cells - Genomics (PubMed)

Cancer stem cells - Ethics (PubMed)

Categories: Stem Cells