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Published online 4 September 2008 | 455, 148 (2008) | doi:10.1038/455148a
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Cancer complexity slows quest for cure
Genomic analysis reveals multiple mutations in tumours.
Hopes that large studies of cancer genomics will justify their high cost by offering a fast-track to cures have been dealt a blow by a series of papers.
The controversial Cancer Genome Atlas, run by the US National Institutes of Health, is analysing genetic and epigenetic changes in cancers.
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I would like to have some mention as to the specific loss to the chromosome by those mutations cited. What duties were these altered genes performing prior to their cancer expression? I am sticking to my simplistic understanding of a cancer expression in terms of what it lacks, linking it to some primordial life form. A cancer cell lacks any symbiotic performance inclination; so this dates it back before such capabilities became a necessary survival function. It kills the host while similar invaders have learned to co-exist. Next, that a cancer cell also lacks angiogenesis codes, suggests, to me, this life form prevailed at a time preceding the evolving of digestive systems. Energy, as nutrition, may have simply been absorbed through the cell lining. Ray Tostado Los Angeles
This problem was foreseen at its beginning. Please read an article "Cancer Genome: An Artificial Creature and an Illogical Concept" at http://im1.biz/albums/userpics/10001/LB2006V6N1A5_cancerGenome.htm OR http://im1.biz/albums/userpics/10001/LB2006V6N1A5_cancerGenome.pdf. Here is just the abstract for this paper:/// A huge amount of money has been set aside for sequencing the so-called "cancer genome". However, this terminology, although highly attractive and timely catches the trend, is actually a very illogical one. Cancer is a disease, not an organism. Creating such an artificial "genome" for sequencing is scientifically wrong. Furthermore, oncogenesis may involve just a tiny part of the whole genome of the various cancer cells (not the cancer genomes). Thus, the whole-genome sequencing of various cancer cells may be unnecessary. An efficient and may be more effective approach to study cancer may be the traditional pathology/biology-based querying, added with selected sequencing of the highly targeted genome areas. The reporting of some convincing experimental evidence to demonstrate the low yield and the high cost of the "cancer genome" approach may reveal just the tip of a huge money-sinking iceberg that may serve well the purpose of a specific group of cancer researchers but not really effectively increase the overall understanding of the cancer biology.///Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1
Better understanding of cancer biology is more important than sequencing a few more "cancer genomes"!!!!! Please read this article "Occurrence of cancer at multiple sites: Towards distinguishing multigenesis from metastasis" (http://www.biology-direct.com/content/3/1/14). Here are just a few "snapshots":/// From an aging perspective, it is very likely the same aging process may result in genetic and/or epigenetic damages to DNA or other molecules in cells located in the different parts of the body which then contribute to the independent origin of CICs(cancer initiating cells) and thus non-metastatic MSCs (multi-site cancers). This parallelism in cell lineage development, in similarity to the parallelism observed in evolution, predict that a common aging-mechanism-based carcinogenesis may explain not only why cancers often occur at the older ages but also why older people tend to have multiple cancers. The detailed hypothesis of a linkage between DNA molecule aging and cell aging and the existence of such aging axis from molecule to cell and to multicellular organism may provide a foundation for drawing a roadmap for not only normal development but also some abnormal processes./// From recent understanding of genome organization it is clear that genomes are composed of various modules. Theoretically, independent mutations can happen by a common mechanism on the same type of DNA module that contributes to different genes or genes' regulatory elements. As a matter of fact, more and more evidences are accumulating to support this mechanism of multi-gene and multi-site mutations/alterations in genome and the subsequent cancer formation. Thus, rather starting a series of primary-secondary cancers from one mutation in one cell, multi-site cancers can originate from multiple mutations/alterations on the same genes/genome locations or the same module in different genes. ///The development of cancer is not just a "seed" problem but also a "soil" challenge. Given that cancer "seeds" could be formed through multiple routes and come in as a result of some early spread, an effective cancer therapy should also include preventing the "soil"-more precisely, morphologically normal, yet likely premalignant cells-from undergoing oncoprotein-driven malignant transformation./// Ideally, highly-targeted cancer drugs should be developed that will be effective only at those proliferating cells bearing the cancer biomarker(s). Certainly, different cancer cells originally from different points of cell lineage formation may have their different biomarkers and thus even cancer drugs themselves should be tailored for the different types of cancers./// Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1
EPIGENETICS: RESPECT A DIFFERENT BUT VERY CORRECT VIEW!!! For those who are still unclear what epigenetics is and how it works for normal differentiation/adaptation and abnormal mutation/oncogenesis, please be modest enough to read some ?side-stream? publications. For example: Respecting Published Answers for Important Questions on Epigenetics (http://im1.biz/albums/userpics/10001/TW2007V2N1A9_EpigeneticsCell.htm OR http://im1.biz/albums/userpics/10001/TW2007V2N1A9_EpigeneticsCell.pdf) A High Time for Understanding the Correct Temporal Order of Epigenetics (http://im1.biz/albums/userpics/10001/P2007V2N1A6_EpigeneticTime.htm OR http://im1.biz/albums/userpics/10001/P2007V2N1A6_EpigeneticTime.pdf) Linking DNA Aging with Cell Aging and Combining Genetics with Epigenetics (http://im1.biz/displayimage.php?album=11&pos=11 ) A Theoretical Framework for Understanding Biotic Aging from Molecule to Organism in Multicellular Life (http://im1.biz/displayimage.php?album=12&pos=3 ) /// Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1
ABSOLUTELY NONSENSE! Many publications in "top" journals have promoted an idea of "inducing cellular senescence to cure cancer". However, this is a deadly wrong approach for treating cancer. Those believed in this therapy either did not understand cancer biology or misunderstood aging. Please be open-minded to read some articles rejected by those "top" journals but nevertheless PUBLISHED. For example, "Cellular Senescence": What Does It Really Mean?( http://im1.biz/albums/userpics/10001/V5_I4_A9_CellularSenescence.htm OR http://im1.biz/albums/userpics/10001/V5_I4_A9_CellularSenescence.pdf ) Suppressing Cancer: Do Not Confuse Inhibition of Cell Reproduction with Cell Senescence (http://im1.biz/displayimage.php?album=14&pos=9 ) Further Evidence for the Emerging Paradigm of an Association of Cancer and Senescence at the Molecular Level (http://im1.biz/displayimage.php?album=18&pos=10 ) Hard to swallow: Oncogenic "pills" for cancer? (http://im1.biz/albums/userpics/10001/LB2006V6N1A4_HardToSwallow.htm or http://im1.biz/albums/userpics/10001/LB2006V6N1A4_HardToSwallow.pdf ) Is STAT3 really a valid target for cancer therapy and should it be? (http://im1.biz/albums/userpics/10001/IM2006V1N1A2_Stat3.htm OR http://im1.biz/albums/userpics/10001/IM2006V1N1A2_Stat3.pdf ) /// Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1
"A cancer cell lacks any symbiotic performance inclination; so ``` " great point of view~~~
Studies on the formation of colonic polyps and synchronous adenocarcinoma provided evidence that the formation of genetic abnormalities precede the development of malignant state. Therefore, just simply linking mutations as a causative factor with cancer is unreasonable. Instead, we should investigate if the observed genetic abnormalities are just a phenomenon rather than the cause of the cancer disease.
Hi, Cancer complexity slows quest for cure. cancer genomic is a complex evolutionary thing, changes happen within hours. To attack this censorious process we knock out the signalling factors that control tumour growth. Looking at genetics is secondary and confusing. Tumour growth factors should be addressed. Regards Dr. Terence Hale
Can genome sequencing really resolve biological puzzles? I still remember that the high praise for Human Genome Project (HGP) ? the Book of Life. Now we have the "complete" or, as we know now the "half" (the haploid part of the duploid) human genome sequence but does this human book of life really advanced much of our knowledge on human life? As a side or front runner products of HGP, many small (microbial) genomes have been cracked open completely. But are we really better off in understanding microbial life? Now, the big Book of Life produced by HGP turned out to be just a tiny piece of human information and we need at least ONE THOUSAND human genomes to have a minimum taste of the human life diversity. The little Book of Life derived from microbial genome sequencing has essentially invalidated our basic assumption of a common ancestor for all lives since the Tree of Life (ToL) really has no Single Root. But we do have many surplus DNA sequencing machines and they are more to be added cheaply to our research capability. So what should we do with this "enhanced" research capability and where to get the money to support this research specialty? More sequencing of genomes! Thus came the various conceptual "genomes" such as "Cancer Genomes", "Diseases Genomes" and even various epigenomes. However, I have to say this, other than burning a huge amount of money, these genome or epigemoe sequencing BIG PROJECTS really have little impact in the history of biology and medicine. That is why HGP even cannot win a Nobel Prize despite some repeated nominations based on its Citation Impact for the prize [See "Why Couldn't Mapping Human Genome Win a Nobel Prize" (http://im1.biz/albums/userpics/10001/V5_I4_A2_NoNobel4HGM.htm OR http://im1.biz/albums/userpics/10001/V5_I4_A2_NoNobel4HGM.pdf )]./// Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1
Clearing conceptual confusions can simplify our understanding of cancer and life. For those submerged too deep in the mainstream and thus still puzzled with the "complexity" of cancer or any other biological or medical problems, please get out of the mainstream and taste the water of some side streams. There were already some simple and direct answers to those "enigmatic" puzzles in biomedicine. For example, Logical Biology and other new-generation scientific journals published by the Truthfinding Cyberpress (http://im1.biz ) have published hundreds of papers elucidating some fundamental aspects of life and diseases. Here are just a few titles related to cancers: Potential of Retinoblastoma Protein to Block Insulin Receptor Activation by Insulin: Structural and Experimental Clues to a Novel Anti-Dogma on a Dual Inhibition of Cancer and Ageing (http://im1.biz/displayimage.php?album=9&pos=6 ) Invisible Field beyond Visible Cells: It Is Time to Jump over a "Berlin Wall" in Cancer Research (http://im1.biz/displayimage.php?album=11&pos=5 ) Disconnecting Cancer Cybernetics Through a Dual Anti-Nucleocrine Strategy:Towards an Anticipatory Therapy of Malignant Disease ?http://im1.biz/displayimage.php?album=11&pos=6 ? Normal Cells First:A Possible Copernican Turn in Cancer Therapy ?http://im1.biz/displayimage.php?album=11&pos=21 ? On Mass, Motion, Speed, Force and Energy in Molecular Biology: Implications for Cancer ?http://im1.biz/displayimage.php?album=11&pos=24 ? Potential Extracellular Roles of the Tumor Suppressor Retinoblastoma Protein (RB): Insulin-Binding Protein and Beyond (http://im1.biz/displayimage.php?album=12&pos=5 ) Suppressing Cancer: Do Not Confuse Inhibition of Cell Reproduction with Cell Senescence (http://im1.biz/displayimage.php?album=14&pos=9 ) Redefining Oncogenes: Distinguishing Real Criminals from Innocent Bystanders (http://im1.biz/displayimage.php?album=15&pos=2 ) Hard to swallow: Oncogenic "pills" for cancer? (http://im1.biz/displayimage.php?album=15&pos=3 ) Cancer Genome: An Artificial Creature and an Illogical Concept (http://im1.biz/displayimage.php?album=15&pos=4 ) /// Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1
Expectedly, genes are just the library, not the ones who read it.. It's all in the behavior of stem\cancer cells, their microenvironment and their genes. Often, viruses are responsible for cancer. However, the peculiar selfish behavior of cancer cells can be a unifying target of many types of tumor, since it is possible to detect solid tumors with a PET scan. Cfr. the book "The selfish cell" for a detailed discussion on these topics.v .
It is true that cancers are not just determined by genes as suggested by the gene-centric views. Cancers are not just stem cell diseases, either. Cancers can happen to many different cells in different stages of the development. They are the results of (broad sense) mutations which include changes in DNA sequences (in coding regions i.e. genes or non-coding regions but not so "junk" DNA) and conformations (from genetic and/or epigenetic processes). These (broad sense) mutations can independently happen at the same time or different times. The use of so-called "clonal" markers to trace the origin of cancers may be misleading because SIMILARITY can be a result of common MECHANISM, not just a common ANCESTOR. Cancer researchers as well as evolution researchers have to realize this fundamental mistake in biology to get a correct picture of cancer or evolution. /// Shi V. Liu, SVL@logibio.com, http://im1.biz and http://blog.sina.com.cn/im1