Cancer

Cancer is one of the most intriguing and frustrating paradoxes of life. Life on Earth evolved because of the susceptibility to mutation that that’s inherent in DNA. DNA is a fragile molecule that is easily damaged. And these are the damages that cause cancer. If DNA wasn’t fragile, though, then evolution wouldn’t happen. This disease, however, seems almost like an inherent element of life as we know it. What causes it? What can we do to prevent is? Can we really cure it? Let’s find out.

Causes of Cancer

It can be attributable in about 80% of cases to external environmental causes. We must understand, however, the inner mechanisms of our bodies that go wrong for it to occur. One of the hallmarks of tumor cells is that they lose control over cell reproduction. I think most people know this, but there are other important defining characteristics of this disease.

There are some tumors caused by viruses. Tumor viruses were discovered in a very interesting way, in 1910 by Peyton Rous.

Inherited mutations in tumor suppressor genes can allow cells to divide inappropriately. It turns out that about 10% of tumors are inherited. This includes about 10% of breast and colon tumors. Compared to non-inherited ones (called also sporadic), inherited tumors typically occur earlier in life. For instance, inherited breast tumors would manifest in women during their 20’s, instead of in their 50’s, as it is common with sporadic cases.

Most cases turn out to be sporadic, so they need many mutations in order for the tumor to form. These mutations are caused by something from the outside. Common causes are carcinogens. They are divided into three groups: physical, chemical and biological agents.

Cancer Statistics

It is interesting to look at the statistics. Thanks to research we know many facts about its incidence and the factors that contribute to it. There is a very strong racial and geographical bias in who gets this disease and who doesn’t.

Cancer treatment

How do we treat and cure this fearsome disease? There are three ways to treat it: surgery, radiation and chemotherapy.

Breast cancer surgery has always been the first line of treatment for this disease, and remains so today, even though is the most invasive one. Surgery is the tool with which we can remove the bulk of the tumor most easily.

A second kind of treatment is radiation therapy. In this case we use high energy coming out of a radiation generator to create a release of energy within the patient’s DNA. Comparing this kind of treatment with surgery, radiation is going to give us excellent control of those microscopic margins, because we aim it in the area where the primary tumor is located, but also is going to have a wider spectrum.

In chemotherapy, we give drugs mostly intravenously. As you may know, within seven seconds they are going to get to virtually every cell in the body. The good thing about chemotherapy is that we don’t need a target. This is why it has become so important in metastatic tumors. We don’t need to know where the tumor cells are hiding, the drugs will get there. However, it is very toxic and it isn’t good for handling tumor bulk.

Cancer Statistics

It is interesting to look at cancer statistics. Thanks to research we know many facts about cancer incidence and the factors that contribute to it. There is a very strong racial and geographical bias in who gets cancer and who doesn’t. The geography is interesting. In Japan, there was a very high risk of gastric cancers probably due to eating lots of smoke foods. That risk is starting to disappear as habits change. There was, according to many cancer statistics, a very low incidence of uterine cervical cancer in Israel probably due to specific sexual practices and circumcision.

If you look at some of the charts of cancer statistics in female population, there is an interesting change in trend in lung cancer. This has to do probably with the advent of the women’s liberation movement, which made it much more acceptable for women to smoke. Lung cancer rose at a dramatic rate.

It is interesting that the incidence of breast cancer stayed about the same, but the death rate from lung cancer now exceeds the death rate from breast cancer. There are more breast cancers still, but lung cancer is much more fatal. There is also a decline in colon cancer because of endoscopy. We started looking at colon cancers through the colonoscope and it turned out we can take out most of them in early stages. Now we are getting to these before they are full blown cancers and we’ve achieved a huge decline in both incidence and death rate.

Lung cancer is very high in Asia, where people smoke much more heavily than in this country. Primary hepatic cancer (cancer of the liver) is very high also in Asia because of a combination of something called aflatoxin. Aflatoxin is a toxin that comes from a fungus and they occur in poorly stored grains. Liver cancer is very common in Asia and Africa, and virtually unheard of in America. Maybe you’ve heard that someone got liver cancer, but I’m almost sure he doesn’t.

There is a difference between primary cancer and metastatic cancer. When a cancer starts, for example, in the breasts, that is called primary breast cancer. When that cancer spreads to the brain or the liver, it is still breast cancer. It’s not liver cancer. It is very rare to see primary liver cancer, meaning that the cancer started in the liver cells.

We see a lot of melanomas of the skin due to ozone depletion in the Southern hemisphere. There is big hole in the ozone layer right over Australia. Cancer statistics start to show a very high incidence of both melanomas and other kinds of skin cancers due to UV light.

There are racial factors in the incidence of cancer. Blacks, for example, are protected from the effects of UV light by the melanin, which are benign cells in the skin that filters out those lights. Skin cancers in blacks are much rarer.

Poverty is also linked to cancer. Just like it is with infectious diseases, it is not very good to be poor.

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What Causes Cancer

What causes cancer? We all know that cancer cells are different from normal cells. One of the hallmarks of cancer cells is that they lose control over cell reproduction. Normally, cells control when and where they reproduce. They do it in two ways. There are internal controls. Normally, there is an internal clock inside a cell that triggers in the cell division cycle.

Most mature(specialized) cells do not divide. Immature cells divide rapidly (think of an embryo or bone marrow). What keeps cells dividing is a group of proteins that stimulate them. What keeps them from dividing is a set of proteins that blocks them from cell division. Because they block tumors from forming, we call them tumor suppressors. These proteins act the control points during cell division.

Cancer cells have defective tumor suppressors. They have mutations in their DNA that causes the protein that normally functions to block cell division to not function. Those are the internal controls of cell division.

There are also external controls in cell division. The external controls are hormone-like substances called growth factors. They stimulate cells to divide by acting like a gas pedal in a car. For example, a blood clot forms and then the wound heals, so the skin around the blood clot heals, and the clot goes away. The cells that surround the blood clot have to be stimulated to do so. Those cells have to surround the blood clot and close the wound. “Closing the wound” is not a biological term, what really happens is a lot of cell division. In turns out that the same cells that form the clot stimulate the cells above it to heal. The clot makes a growth factor that stimulates the skin cells to divide, reproduce and heal the wound.

Genes whose protein products stimulate cell division in this way are called oncogene. Cancer cells usually make their own growth factor. They would have an oncogene that is mutated, so it is producing constant stimulation for cell division. Other cancer cells may have genetic changes that make them hypersensitive to even tiny amounts of growth factors. These are the genes that turn on the gas pedal of cell reproduction.

The most fearsome aspect of cancer is that cancer cells can spread to other organs. This is called metastasis. You can’t do surgery if a tumor is all over the place. This leads to multiple organ failures, and it is really what often causes people to die of cancer.

Normal cells have a “glue” that causes the cells to stick to one another. This glue is specific. If you pinch your skin, you will notice that the cells at the skin stick together and are separate from the bone. They must have a specific “glue”, which is formed by proteins. There are cell recognition and adhesion proteins. Cancer cells loose this adhesion.

There are several steps in metastasis. First, cancer cells have to loose their adhesion and detach from the tumor. Then, the cells make it to the bloodstream or lymph system. In the blood, they travel to an organ. They stop at the new organ and grow as a satellite tumor. We know all of these steps in great detail at this point.

This events: inactivation of tumor suppressors, activation of oncogenes and metastasis; occur in sequence. Cancer is a multi-step disease. To be continued…

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