The cells being described are pre-cancerous. Once they go over the red-line and become cancerous, the body's immune system works at removing them. The failure of the immune system to destroy cancerous cells appears to be the true nature of cancer's rise. One category of new drugs, the ones that target the programmed cell death mechanism, inform this view. T Cells are unable to tell cancerous cells to die (apoptosis) when the PD receptor mechanism is jammed. Or, cancerous cells aren't attacked because they don't look cancerous. The CAR-T approach adds a new 'chimeric antigen receptor' = CAR to a T cell that helps the T cell find cancerous cells that were invisible to it before hand. I have read that elephants have many times as many oncogenes than we do (hence, much lower incidence of cancer). It would be insightful to sequence their DNA, and see if the prevalence of precancerous cells was as high as humans.
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Carl Zimmer addresses "the smallest living things" by mining the imagination of scientists involved and uninvolved in research that studies tumor cells and the genetic characteristics of these tiny things - as they all scramble on the skin and within the esophagus and elsewhere - and cancer develops or is suppressed... with the interaction of the smallest living things. He addresses ambient radiation and the sun, aging, alcohol, tobacco and other agents that can alter the behavior of the smallest... without addressing the "smallest non-living things" that seem to impact all of it... from space. Einstein addressed particle physics, dark matter, black holes, energy and light - with his imagination. Microbiologists seem to stuff their imagination. Money drives science these days. Microbiome microbiologists and Harvard Medical School are financed by drug companies and government. Until we study the impact of these funders, we will not understand why they will not examine ORAL use of drugs.. any drugs. PARENTERAL and SUBCUTANEOUS are the words I wish to read in medicine. Two illnesses require oral use of antibiotic. Only two. Our immune system is under attack. We are killing our microbiome with what we swallow. Ambient radiation ages us. Genetics and cell biology fight back. We must treasure the gut biome. Zimmer: say that. Ask Hua Helen Wang PhD at OSU what she knows. Publish her findings and her questions. Start with Hua Helen Wang PhD... she researches the needle vs. the mouth.
2
Carl Zimmer addresses "the smallest living things" by mining the imagination of scientists involved and uninvolved in research that studies tumor cells and the genetic characteristics of these tiny things - as they all scramble on the skin and within the esophagus and elsewhere - and cancer develops or is suppressed... with the interaction of the smallest living things. He addresses ambient radiation and the sun, aging, alcohol, tobacco and other agents that can alter the behavior of the smallest... without addressing the "smallest non-living things" that seem to impact all of it... from space. Einstein addressed particle physics, dark matter, black holes, energy and light - with his imagination. Microbiologists seem to stuff their imagination. Money drives science these days. Microbiome microbiologists and Harvard Medical School are financed by drug companies and government. Until we study the impact of these funders, we will not understand why they will not examine ORAL use of drugs.. any drugs. PARENTERAL and SUBCUTANEOUS are the words I wish to read in medicine. Two illnesses require oral use of antibiotic. Only two. Our immune system is under attack. We are killing our microbiome with what we swallow. Ambient radiation ages us. Genetics and cell biology fight back. We must treasure the gut biome. Zimmer: say that. Ask Hua Helen Wang PhD at OSU what she knows. Publish her findings and her questions. Start wit
1
This interesting and thought provoking article ends with an assertion that I feel needs rebuttal as it reflects the continued misinformation and ignorance when it comes to the potential therapeutic effects of whole cannabis derived therapies still being taught in medical schools and held by a majority of physicians, even in States that have long had State regulated medicinal cannabis programs. After describing how these research findings suggest the possibility that tissues with high numbers of cells with oncogenic mutations are kept healthy by competitive metabolic and growth signals, Dr Martincorea says “There is no therapy being thought out in such terms today.” However, the entourage model of competing stimulating and suppressing effects of different cannabinoid molecules binding at different receptors within the same cell or tissue is increasingly being born out in both laboratory and animal model studies. Once the unscientific prohibition of cannabis in the US is finally abandoned, and human studies of “balanced” extracts from whole cannabis plants deemed acceptable by the FDA, we may finally come to appreciate how this plant can stabilize basic cellular and tissue growth and metabolic processes in so many areas of disease pathogenesis, prevention and treatment.
10
Has Mr Zimmer selected the figure that goes with this article? Are those ridges present in the epithelium of the esophagus? Also, from this narrative ("Cancer is a disease of mutations.), in which the same "cancer" mutations appear in otherwise normal cells, would it be reasonable to conclude that in fact mutations play not role at all in cancer? Otherwise, can Mr Zimmer or Dr Martincorena explain how the sizable investment made on this assumption for many decades keeps on generating paradoxes and no answers? Yes, I know... It's a long story...
2
Very nice summary of some brilliant research. The next step may be to find the commonalities of mutant-but-cancerous cells and compare against mutant-but-non-cancerous cells.
Nevertheless, cancer has proven to be far more complex ailment which has led us to research ageing at a genetic and molecular level.
Bravo to researchers whose tireless work gets us one step closer to understanding the disease. Hopefully, one day we will find an effective cure to this very cruel disease.
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For those interested in understanding this area, I highly suggest two short modern classics also from Science, both by Tomasetti & Vogelstein:
“Variation in cancer risk among tissues can be explained by the number of stem cell divisions,” PMID 25554788, at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446723/pdf/nihms686386.pdf
&
“Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention,”
PMID 28336671, at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852673/pdf/nihms940482.pdf.
Appreciate that different cell types in the body have different average lifetimes before apoptosis, their “programmed” cell death—and their need to be replaced. This replacement is done by special stem cells and the cell duplication during this process is when potential-cancer-causing DNA replication errors can occur to either special “proto-oncogenes” or “tumor-surpressor” genes. (Proto-oncogenes control cell division or apoptosis, while tumor-surpressor genes, also called “antioncogenes,” fix mutated genes.)
When enough of these “driver” mutations occurs, you create a cell with fast, uncontrolled growth, i.e. a cancer. (Many researchers believe that only three such driver mutations are necessary to create a cancer, not “five to 10,” but it depends on which.)
An important implication of cumulative DNA replication errors is that most (maybe 2/3?) cancers are the result of random “bad luck.”
(This is controversial because of implications for future cancer research funding.)
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@SRP. “bad luck.” - But the percentage of “bad luck” increases dramatically with exposure to the environment - such as what you eat, drink, breathe, smoke, bathe in, exposed to, .... No controversy here.
4
Isn't this simply a matter of penetrance? And we know why diseases show reduced penetrance - variable genetic background - so why doesn't this extend to the cell and cancer?
this article lends credibility to the theory that restrictive lifetime calorie intake will not only help one live longer but will result in a "healthier" self, as calorie restriction slows one's metabolism resulting in slower cell regrowth. Slower cell regrowth and cell reproduction result in less cell mutations and, thus, less risk of reproducing mutated, damaged cells..
11
We are still in the stone ages with medicine, only a little bit past alchemy and leeches. We still think of cancer as the tumor itself, the cells growing uncontrollably. But in fact the tumor is only the symptom; the disease is a control system that is malfunctioning. No wonder cancer medicine is so ineffective -- we spend all our resources removing and killing tumors without understanding why they occurred in the first place. Maybe in another 400-500 years we'll have it figured out.
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The new area of Epigenetic Medicine has merged with the information provided in this article to reveal a world we could only dream of years ago.
Understanding gene expression provides new ideas for using natural methods powerful in correcting mutations.
There are stategies for combating the aging damage done to DNA . For example, certain enzymes in fresh fruit and vegetables have been shown to go up and down mending our DNA . This expains why some cancer therapies may have been successful using fresh juicing and other nutritional approaches. (Gerson Therapy, Dr McDougall, Dr Fuhrman)
Certainly a lifestyle encouraging this new science should replace our old model of exclusively relying on chemo...but this update could take decades.
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There are several explanations for the phenomena of our cells exhibiting genetic mutations that are "pre-cancerous," but which do not develop into cancers or lesions.
Foremost is that for various reasons these cells are identified and tagged for disposal by our own immune systems during daily 'housekeeping' activities.
Then there are specific factors like the cMet receptor that stimulates or regulates as a switch that is normally locked in "off" position; the processes of cell motility, invasion and metastasis. It's ligand (molecular bonding position in the genome) is associated with HGF- human growth factor and development of embryos, and specific tissues and organ growth - tubules, liver tissue, lungs, etc. There is a great deal of current research focused on regulating or 'turning off' this tyrosine kinase inhibitor in cancer patients where it is a significant presence found in their lesions or blood.
There are are a numerous tyrosine kinese inhibitors either in trial, or approved for use for blocking certain nutrient pathways certain mutation expressions exploit for their rampant reproduction.
The research highlighted by this article could mislead those prone to 'cancer hysteria' to embrace crackpot prophylactics offering 'preventative therapy.'
Emphasizing multi-path testing of combination therapies in an approach similar to the one adopted with success against HIV is likely a more productive avenue in finding ways to prolong productive lives as we age.
28
@jwp-nyc I am a cancer 'survivor', having DLBC cancer for 14 years, stem cell transplant 7 years ago. I am now on Imbruvica, which coincidentally IS a tyrosine kinese inhibitor. It is almost $10,000 per month. In the 9 months I have been on it my cancer has been frozen in place, at low level.
2