Cancer: An Unwanted Guest

Jabale Rahmat

Freshman

School of Life Sciences

Independent University, Bangladesh

May 26th, 2017

Lamia, a middle-aged woman, is sitting in the waiting room of a clinic with a receipt in her hand. She is waiting for her number to be called to collect her mammography report. She is watching the preview window which shows the call number for the next patient. When her number comes, she stands up with fear on her face. She moves toward the reception desk and collects her report. She is scanning the report with frightened eyes and praying to God for a negative result for breast cancer.

If just the possibility of cancer can be so frightening, how much more suffering will come from a positive diagnosis?

“Cancer”, the word, carries a lot of weight. The disease, cancer, has an effect on both the person and his or her family. Cancer patients are not only devastated by physical pain, but their mental health also gets affected due to the economic burden that they have to bear. A cancer patient essentially becomes a prisoner from the moment they are diagnosed.

How does cancer develop? Cancer at its root is a genetic disease, caused by mutations after birth that cause abnormal cell division. Cell division is a process by which a single cell multiplies into two. From growth to the replacement of dead cells, cell division plays a vital role in all living organisms, including human beings. When we cut our hair, new hair grows through cell division. Millions of red blood cells die in our bodies every day and new blood cells are generated through cell division.

There are many factors that affect cell division. Cell division is not a random process. When a cell receives a certain signal, the cell divides. Cells in the heart hardly divide unless there is any abrupt change, for example cell death. To compensate for the loss of dead cells, a signal is sent from nearby cells, which in turn triggers a cell to divide and replace the lost cells. Therefore, cell division is a “programmed” process. Unlike healthy cells, cancer cells divide randomly and continuously – i.e. cell division in cancer cells is a broken program.

Experiments have shown that cultured human cells can only grow outside the body if special chemical growth factors (normally produced by human tissues) are added to the nutrient broth. But cancer cells are often able to grow on simple nutrient broth that completely lacks any added growth factors. This suggests that cancer cells manage without the growth factors that are necessary for normal cells to grow inside organs and tissues. Thus, the question arises – how do the cancer cells manage to divide without growth factors?

Probable genesis of cancer. Stanford

The program for cell division is contained within the genetic content of a cell. When a cell reproduces, the contents of that cell reproduce as well. During normal cell division, several genes are involved in making sure that the cell has enough resources to divide into two cells. Genes are made up of DNA. DNA molecules are very inert, that is, they are resistant to many chemical reactions, but they can still get damaged when they come into contact with certain chemicals. We call these chemicals carcinogens. Cigarette smoke is a potent carcinogen that can damage DNA molecules when inhaled. The DNA damage can result in mutations that trigger abnormal cell division by affecting genes that are involved in regulating cell division. This in turn can result in cancer.

The genes which cause cancer when damaged can be characterized as either proto-oncogenes (genes whose activity normally promotes cell division) or tumor suppressor genes (genes that normally prevent cancerous cell division in healthy bodies). I will discuss some examples of these genes below.

Under normal circumstances, proto-oncogenes induce cell division, and then stop. Mutations in proto-oncogenes can transform them into oncogenes that cause continuous cell growth. HER2 is a proto-oncogene that in its mutated, oncogene form gets overexpressed in many types of cancer cells, and makes them hypersensitive to very low levels of growth factors. Growth factors mediate their effect by binding to receptor proteins present on the surface of the cell. When they come into contact with the growth factors, these receptor proteins cause chemical changes inside the cell that trigger cell division. HER2 encodes one such receptor, and overexpression of the gene results in the presence of large amounts of receptors on cancer cell surfaces, which is what makes them hypersensitive to growth factors. This causes the cells to divide uncontrollably. Some mutations in HER2 can also induce cell division without the presence of the growth factors. In other cancers, researchers have seen that cancer cells can start to produce their own growth factors, leading to cancerous cell proliferation. Many oncogenes cause cancer in this manner by reducing the dependency of cancer cells on external growth factors.

Even though our body is constantly exposed to carcinogens, for instance in the form of UV radiation in sunlight, this does not result in cancer in the vast majority of cases. This is because tumor suppressor genes like TP53 can respond to the DNA damage caused by carcinogens and prevent the development of cancer cells. For example, p53, the protein encoded by the TP53 gene, can respond to DNA damage by triggering apoptosis, a form of programmed cell death, and clear tissues of potentially cancerous cells.

But what happens where is a mutation in the TP53 gene itself? This can be caused by DNA damage caused by carcinogens like cigarette smoke. This will impair the gene’s ability to identify and respond to further DNA damage in the future. Thus, the unwanted guest, cancer, can enter. Normally, multiple mutations of the types we discussed need to occur before cancer arises.

Some people may have increased risk for certain forms of cancer due to the presence of some mutation that they inherited from their parents. But it is always true, regardless of whether a patient inherited genetic risk factors from their family, that all forms of cancer are genetic diseases caused by mutations in cellular DNA.

Despite this increased understanding, to this day there is no permanent cure for the disease. Millennia after its discovery and after a century of biomedical research, scientists have made incredible progress in treating cancer, but many forms and stages of cancer remain untreatable. There are also many moments when physicians think that they have cured a cancer patient fully, only to find that a few months later the same patient comes back with a powerful and resistant form of the disease. The disease can be cured but not its successors.

The war against cancer is an ongoing struggle that brings together patients, oncologists, and biomedical researchers. Chemotherapy results in the evolution of resistant cancers, forcing researchers and oncologists to come up with new technologies and strategies. This war is not new, but has been going on for thousands of years. Until scientists can develop reliable permanent cures, the war against cancer will never end, and people like Lamia will have to live with the fear and possible trauma of cancer.

Jabale is a Fresher in the School of Life Sciences at IUB majoring in Biochemistry. He is a future scientist who is crazy about everything related to biology, especially genetics.