Cancer is something that is extremely scary and is unfortunately becoming more commonly diagnosed. With many referencing “coming up with the cure to cancer” as something futuristic and groundbreaking, it seems that a lot of people look over the fact that we already have ways to cure cancer, one such way being chemotherapy.
The history of chemotherapy is rather grim, with it originating from the observed effects of mustard gas on soldiers who were exposed to it during WWI and WWII. Upon examination, it was found that the mustard gas had killed white blood cells that were dividing quickly. What makes a cell cancerous is its lack of mitotic control. Normal cells only divide when they receive specific signals, but cancer cells will just keep dividing. Hence, the results made scientists speculate whether the mustard gas would have the same effect on cancer cells. After many years of research and clinical trials, the first chemotherapy drug, mechlorethamine, was created to treat lymphoma, and many followed after.
While different chemotherapy drugs have different mechanisms of action, the main point of chemotherapy is to stop cell division or kill cells undergoing mitosis.
The different chemotherapy drugs can be divided into several main categories and may not be exclusive to anyone.
Alkylating Agents
These are the more common chemotherapy drugs and also the group that nitrogen mustard is in, although not as dangerous nowadays. They form covalent bonds with electron-rich atoms, particularly nitrogen, found in many biological molecules like amino acids, RNA (ribonucleic acid), and, more importantly, DNA (deoxyribonucleic acid). Many know DNA contains the cell’s genetic information, making it extremely important for mitosis. Alkylating agents can be bifunctional or monofunctional. Bifunctional agents crosslink parts of a DNA strand to another part of the DNA strand, disrupting the structure of the DNA. Monofunctional agents cause the DNA to be methylated, resulting in spontaneous and enzyme-mediated single-strand breaks. Both methods result in the DNA being heavily damaged, preventing the cells from undergoing mitosis and their death.
Antitumor Antibiotics
Unlike regular antibiotics that target bacteria, these target cancer cells. These drugs work in many ways, like DNA intercalation, Free radical formation, DNA Adduct Formation, and enzyme interaction. DNA intercalation involves the drug inserting itself between DNA base pairs, disrupting the DNA structure and processes of replication and transcription, resulting in cell death. Free radical formation consists of generating reactive oxygen species that result in oxidative damage of various biological molecules in the cell, like DNA, resulting in cell death. These antibiotics can also bind to enzymes like topoisomerase-II and ribonucleotide reductase, which are crucial for DNA repair and synthesis, disrupting DNA. The formation of DNA adducts would block specific transcription factors from binding to the DNA, resulting in cell death. Anthracyclines are a notable class of antitumor antibiotics. They are extracted from types of Streptomyces bacteria and are associated with cardiomyopathy hence, there is a limit to doses that can be given to patients.
Antimetabolites
Unlike the previous drugs, these do not mainly affect the DNA itself but the components of DNA, the nucleotide bases. They cause the depletion of nucleotides and can also be mistakenly included in DNA as a nucleotide base, resulting in damage to the DNA.
Topoisomerase inhibitors
Topoisomerases are an enzyme that untangles DNA, making them important in DNA replication, transcription, chromosome segregation, and recombination. This makes them good targets when trying to prevent cancer cells from dividing.
Mitotic inhibitors
Commonly derived from natural substances like plant alkaloids, they bind to microtubules, essential structures used during cell division and prevent their polymerization. This results in the dividing cell being halted at the metaphase stage of mitosis, preventing the cell from completing mitosis and inducing cell apoptosis after the arrest has gone on for a while.
This is excellent news for us since, as mentioned before, cancer cells like to divide. This is also bad news for us since our normal cells will also divide, although not to the extent of cancer cells. This does mean that chemotherapy can come with infamously horrible side effects, with a drug, doxorubicin, even being branded as the “red devil” due to its potential side effects and distinctive color.
The most well-known effect of chemotherapy is alopecia, the loss of hair. This is because cells involved with hair follicles also undergo cell division frequently and, hence, are targeted by chemotherapy. It is important to note that while many chemotherapies can result in hair loss, not all would. The hair does grow back after treatment, although it can be changed, with it going from straight to curly or even being of a different color.
Another common side effect is the decrease in white blood cells in one’s body since chemotherapy also targets them. Hence, doctors need to check their patients' white blood cell count before giving chemotherapy so that the patient does not get neutropenia, the term for when the quantity of white blood cells in one’s body is insufficient. This is why chemotherapy patients should be mindful of their surroundings and the types of food they eat since they have lowered immunity and are more prone to infection.
Chemotherapy does not have the best reputation, but it is still the first line of treatment for many types of cancer and has been successful in managing and even curing the disease. With increasing research in the field, one can be hopeful that this treatment can be further improved. For now, it is important to destigmatize chemotherapy and those undergoing it, showing our support and care to those fighting against cancer.
Reference List
American Cancer Society. “History of Cancer Treatments: Chemotherapy.” Www.cancer.org, 12 June 2014, www.cancer.org/cancer/understanding-cancer/history-of-cancer/cancer-treatment-chemo.html.
Europe PMC. “Europe PMC.” Europepmc.org, 2016, europepmc.org/article/NBK/nbk538187#__NBK538187_dtls__. Accessed 6 May 2024.
Kufe, Donald W, et al. Holland Frei Cancer Medicine 7. Hamilton, Ont. ; Lewiston, Ny Distributor, Bc Decker, 2006.
Lansiaux, Amélie. “Antimetabolites.” Bulletin Du Cancer, vol. 98, no. 11, Nov. 2011, pp. 1263–1274, https://doi.org/10.1684/bdc.2011.1476.
Nitiss, John L., et al. “Topoisomerase Assays.” Current Protocols in Pharmacology, vol. CHAPTER, 1 June 2012, p. Unit3.3, www.ncbi.nlm.nih.gov/pmc/articles/PMC3397423/, https://doi.org/10.1002/0471141755.ph0303s57.
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