How does cancer arise?

I’ve already dedicated a post (here) to describe how frequent tumors are. In this post I will focus instead on how tumors arise. We know that viruses and bacteria are responsible for nearly all diseases, but cancer (with few exceptions). So, if viruses, bacteria, or parasites are not the main cause of cancer, how do tumors arise? The short answer is that cancer arises when DNA inside a cell is mutated. Does any DNA mutation cause cancer? The answer is no, and now we will see why. If you missed my previous post about cancer, I recommend you to read it here, to find answers to many common questions.

I will answer the question while we take a ride by car. Imagine we are on a motorway. On motorways you cannot neither overcome speed limits (quite obvious), nor drive too slow. It is important that during our journey we don’t hit any other car, and we respect all the rules we were taught at the driving school. Now, imagine that we are a cell, and the motorway is the human organism. A cell receives signals from the organism (for us it would be the signs on the street), and it needs to respect them, together with all the other cells. But what happens if a cell ignores these rules? If on the motorway we find a speed limit of 70 mph, but we drive at 100 mph, we break a rule and the police would intervene. Yet, we continue our ride, while chased. Sooner or later the motorway would undergo some trouble, because we would cause accidents with serious consequences. This is what happens when a cell undergoes cancer transformation. It would proliferate uncontrollably, ignoring the signal to stop coming from the organism, messing it up. Now let’s look closer at the cause of our mad race. A cell doesn’t decide spontaneously to become a tumor cell, but some unwanted mutation has to occur to begin the process. In fact, we were exceeding the speed limit because our accelerator broke, and we couldn’t control the car anymore. Another problematic situation would arise if the brake would break. In this case we would not overcome the speed limit, but instead we would cause an accident if the car in front of us suddenly slows down. The accelerator represents the proto-oncogenes of a cell, while the brake pedal symbolizes the tumor suppressor genes. Proto-oncogenes are a gene family that promotes cell growth. These genes need to be silenced to prevent uncontrolled proliferation of the cell. If a proto-oncogene is mutated, it becomes an oncogene and it would act like our broken accelerator. Tumor suppressor genes are instead a group of genes which negatively control cell growth and maintain quiescence, and if one of these genes is mutated, the cell would continue proliferating when instead is supposed to stop. There is a last group of genes involved in cancer transformation: the ones responsible for DNA repair. Suppose that our accelerator or our brake stops working properly, but we are able to fix the problem before our car causes any damage. This is what DNA repair genes are responsible of. These genes are able to repair mutations of DNA, thus preventing any dramatic consequence in the cell.

I guess now you can understand why tumors always carry at least one gene mutated belonging to one of these three categories. Any gene can undergo mutations, of course, but if it is not involved in cell proliferation, its mutation will not contribute to tumor transformation, but to some other disease, depending on its biological role. Usually cancer cells carry several DNA mutations, because after the first one occurs, all the control/repair processes stop working properly, and mutations continue accumulating. Imagine a motorway where hundreds of drunk drivers are riding cars with accelerator and/or brake broken. That’s how a proliferating tumor behaves in the organism.

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