What is Cancer?
What is Our Present Model of Cancer?
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Cancer is a disease of single cells that have accumulated genetic mistakes (mutations).
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Thirty years ago only a few cancer causing mutations had been identified. These resulted in overactive "ON SWITCHES" (Oncogenes) and disabled "OFF SWITCHES" (Suppressor genes).
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The simple model of a cancer cells was conceived, in those days, to be like a car with the accelerator jammed on and the brakes not working.
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A key way in which cancer cells behave is by unrestrained proliferation and the discovery in the early 1970s, of the way that cell division was controlled, added the engine to the model of the "cancer car".
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Despite having an engine, deficient brakes and a jammed-on accelerator, to be able to career dangerously down the road, the cancer car would also need petrol to supply energy.
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Over the years it has become increasingly confirmed that cancer cells use energy in a different way to normal cells. This altered carbohydrate metabolism was first reported by Warburg one hundred years ago.
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​Cancer cells use aerobic glycolysis to produce the energy molecule ATP. This provides the equivalent of petrol as a fourth component of our present model of the cancer cell.
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​Following the completion of the Human Genome Project and with continued advances in High Throughput DNA Sequencing, cancer cells have been revealed to have massive DNA damage.
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Over ten years ago it was known that an individual cancer cell could contain have over 10 different mutations and these might not be the same mutations as those in the cell next to it.
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The variable distribution patterns of cancer mutations within a tumour and between different tumours even if they apparently arose in the same site is termed tumour heterogeneity.
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In addition once the cancer process has started, DNA instability occurs which increases the probability of further mutational errors.
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In normal cells, if small errors in DNA cause malignant transformation, the new cancer cell which is created commits suicide by an active energy dependent process called apoptosis.
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A further feature of our present model of the cancer cell is that, even despite the massive DNA damage it has accumulated later in its development it is still able to avoid apoptosis, unlike normal cells.
Further Progress
In order to make further progress in cancer a broad look is required at everything we have learnt from the multiple approaches to this disease over the past century. Just pursuing one or other particular approach because it is popular is unlikely to ultimately prove successful. Cancer cells exhibit a vast number of genetic mistakes providing multiple tempting opportunities for interesting scientific pursuit.
Research directed at the science within these mistakes may lead to plentiful publications but can be illusory. Don Quixote jousting with windmills. There is a need to stay focussed on looking at the minimal data sets that cancers need to survive. For that reason, my research over the past thirty years has consistently been directed at observing differences between highly genetically damaged cancer cells and normal diploid cells without genetic mistakes.