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Side effects

WHY DOES CONVECIONAL CHEMOTHERAPY HAVE SO MANY SIDE EFFECTS?

One of the main reasons that led to the creation of Prospera Biotech was to help all those people who suffer from skin sensitivity as a consequence of medical treatments. Cancer treatments, while becoming less invasive and more effective, can cause a multitude of side effects that alter the daily lives of people under them. In today’s post we explain why conventional chemotherapy causes so many side effects.

What is a cancer cell?

The human body is made up of billions of cells. Each one has a specific function that develops methodically throughout its life. When cells are damaged in a way that incapacitates them to perform their function, there are regulatory mechanisms that, as if it were a machine, attempt to repair it. However, if the damage is severe and these repair mechanisms fail, the cell, unable to perform its function, dies and is replaced by a healthy one.

Tumor cells arise when a healthy cell accumulates mutations in its DNA that promote their loss of function and the acquisition of an abnormal proliferation ability. We could say that the transformation from a healthy cell to a tumor cell implies a change in function: from carrying out an action necessary for the proper functioning of the body to growing indiscriminately. If they also acquire invasive capacity, we would be facing a malignant tumor or cancer. Neoplastic cells minimize any action that is not aimed at acquiring nutrients or energy that serve them to continue dividing (1).

How do traditional chemotherapy treatments work?

As we mentioned before, under normal conditions, when a cell is unable to perform its function, it dies. Therefore, it seems logical to think that, if a tumor cell is unable to divide, it will die. That’s exactly what most treatments known as chemotherapy try to do. These treatments are chemical agents that by various means prevent tumor cells from dividing properly and therefore induce their programmed death or apoptosis.

For instance, treatments derived from taxane, such as paclitaxel or docetaxel, or treatments known as vinca alkaloids (vinblastine, vincristine…) prevent the correct formation of microtubules. These structures are essential for cell division and, therefore, defects in their formation lead to the interruption of mitosis (cell division) and cell death (2). On the other hand, alkylating agents (such as chlorambucil, melphalan) cause DNA damage (alkylation) which  implies the destabilization of this molecule and avoids its replication (3). Another example of chemotherapy treatments would be the molecules known as antimetabolites. These are molecules very similar to metabolites that are essential to the organism. Hence, cells incorporate them, but once inside these molecules exert a harmful action. In this group we can find, for example, 5-fluorouracil that prevents the genetic material from being replicated (4).

Generally, all these drugs cause disturbances in tumor cells that prevent their division and end up inducing their death. Repeated doses can completely wipe out the tumor cell population.

These treatments could be applied both before and after surgery. If it is done before, tumor reduction or even complete removal could be achieved. When these treatments are applied after the operation they serve to eliminate cells that could not be removed during surgery or those that may be “hidden“.

Why do these treatments have so many side effects?

In the human body there are some organs that need a population of cells that proliferate quickly and in a controlled manner. They are mainly cells from organs that are usually in contact with external or harmful substances such as epithelial cells in digestive organs or skin. These cells carry out mainly protective functions.

Cells of the epidermis form the first entry barrier in our body and renew relatively quickly. In fact, many professionals recommend exfoliating the skin from time to time to help remove dead cells and facilitate the replacement with new cells that will perform their protective function. The same occurs for the cells forming the linings of the mucous membranes. In the stomach, for instance, there is a layer of cells that are in contact with food and gastric juices. These cells are able to withstand the extreme acidity conditions that occur in the stomach during digestion and prevent the damage it could cause in other cells or organs. Being subjected to such conditions requires constant renewal. Therefore, in the human body there are essential cellular populations of rapid proliferation. The difference between these cells and malignant tumors is that the healthy cells grow in a controlled and programmed way in response to a physiological need. The almost continuous renewal of these cellular populations ensures proper protection of these organs and the maintenance of cellular balance.

Chemotherapy treatments spread throughout the body acting on tumor cells but also on many other healthy cells and causing the known side effects. In the case of epithelial cells mentioned above, these drugs prevent their division resulting in digestive problems (nausea, diarrhea, indigestion…), hair loss or skin dryness.

Immune system cells may also be affected by chemotherapy treatments. A reduction in the population of these cells results in the effect known as immunosuppression that getting infections easier. The decline in the blood cell population can also lead to bleeding.

Fortunately, the action of chemotherapy is only irreversible for tumor cells, so after a few weeks, most of these symptoms disappear. Thanks to the action of stem cells, the cell populations of the affected tissues can be regenerated.

In Spain, according to data from the Spanish Association Against Cancer, more than 250,000 people with cancer were diagnosed in 2019 and based on the trend of recent years, the number of diagnoses is expected to increase each year. It is, therefore, necessary to develop strategies that are efficient stopping the progression of this disease, although this may lead to some side effects.

However, the scientific community strives to find new drugs that are able to target tumor cells specifically without interacting with the rest of the body healthy cells. Currently, many of these strategies are being used or in very advanced stages of development.

REFERENCES

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
  2. Manfredi, J. J., & Horwitz, S. B. (1984). Taxol: an antimitotic agent with a new mechanism of action. Pharmacology & Therapeutics, 25(1), 83–125.
  3. Connors TA. Alkylating agents. Top Curr Chem. 1974;52:141-171.
  4. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330-338.
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