CoachA cancer is a population of cells that divide without the controls that limit the division of normal cells, and that invade the surrounding tissues. It begins with one cell whose DNA has accumulated mutations in the genes controlling the cell cycle; the cell’s descendants form a tumour. A tumour that stays confined is benign; one whose cells invade neighbouring tissue and travel through the blood or lymph to found new tumours elsewhere (metastases) is malignant.
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Example 17.4 (Two familiar genes)
A receptor for a growth signal sits in the membrane of many cells; one substitution in its gene makes it signal continuously, without any signal outside — an oncogene found in a third of colon and lung cancers. The gene of p53, on the other hand, is inactivated by mutations in every possible way: substitutions that alter its shape, deletions, a premature stop. A cell that has lost p53 does not stop to repair its DNA before copying it, so it accumulates further mutations faster: losing that brake accelerates the whole process.
Example 17.7 (Tobacco)
Smoke carries some seventy carcinogens; benzopyrene, once activated by the cells’ own enzymes, attaches to guanines and causes substitutions at those positions. The p53 gene of a smoker’s lung tumour typically carries exactly such a substitution, at one of a few positions where benzopyrene binds most readily — the mutagen leaves its signature in the sequence. Lung cancer was a rarity before cigarettes; smoking causes nine cases in ten, and stopping halves the risk within ten years, because the cells that carried the early steps are gradually replaced.
Example 17.10 (Treatments and what they target)
Surgery removes a tumour that has not spread. Radiotherapy breaks the DNA of cells in the beam beyond repair, killing dividing cells preferentially. Chemotherapy uses drugs that block replication or the spindle (Chapter 12): tumour cells, dividing constantly, die faster than normal cells — but the fast-dividing normal tissues (bone marrow, gut lining, hair roots) suffer too, which is where the side effects come from. Newer treatments target the specific mutant protein of a tumour, or unleash the immune system on it.