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Chemotherapy: From Chemical Warfare to Cancer Treatment

Written By: Alex Liao

cancer cell

Cancer

Cancer is a genetic disorder that causes the uncontrollable and abnormal growth of body cells. This is caused by mutations that occur through the growth and multiplication of body cells through a process called cell division or mitosis; damage to DNA by harmful substances or inheritance. This is why cancer is more prevalent in older individuals as mutations build up over time and as well as their degraded ability to eliminate cells with damaged DNA increasing risk. These abnormalities in cell growth multiply with time and develop into tumors, lumps of tissue, which could either be benign (non-cancerous) or malignant (cancerous).


Benign tumors don’t spread and usually don’t grow back once removed; however, some could still cause symptoms that are life threatening if it were located in a vital and susceptible area such as the brain.


Malignant, unlike benign, tumors could sometimes grow back once removed and also spread and multiply to and in other parts of the body forming new tumors in a process called metastasis, developing into metastatic cancer. This affects the body’s functionality and also uses up the body’s nutrients.



Environmental factors that cause cancer

  • Tobacco usage

  • Obesity

  • Excess alcohol consumption

  • Viral infections (EBV, HBV, HCV, HIV, HTLV-1 etc.)

  • Chemical exposure (Benzene, Asbestos, Vinyl Chloride, Radon, Arsenic etc.)

  • Radiation exposure (X & γ rays, α & β radiation, UV rays via the Sun)



Types of cancer (general overview)

  • Carcinomas are the most common type of cancer and are formed by the epithelial cells.

  • Sarcomas are cancers that form in bone or soft tissues such as muscles, fat, blood vessels, lymph vessels, and fibrous tissue.

  • Leukemias begin in the blood-forming tissue of the bone marrow. Large numbers of abnormal white blood cells (leukemia & leukemia blast cells) that build up in the blood and bone marrow causes a low-level of blood cells, thereby reducing oxygen transport and the bodies ability to control bleeding and fight infections.

  • Lymphomas begin in lymphocytes, disease fighting white blood cells, causing abnormal lymphocytes to build up in lymph nodes, lymph vessels, and other organs.

  • Melanomas begin in melanocytes, cells that produce melanin (pigmentation), and form mostly on skin but could also form on tissues



How chemotherapy originated

The origins of chemotherapy were the result of accidental findings during World War I as well as years and years of rigorous research. Sulfur mustard (C4H8Cl2S), or mustard gas is a chemical agent synthesized by Frederick Guthrie in 1860 and is still used to this day in warfare. It was responsible for 1.2 million non-fatal casualties and 90 thousand deaths in World War I. Mustard gas is a dose-dependent agent, meaning its toxicity depends on the level of exposure, and thus its effects range from minor skin irritation to severe lung damage.


chemotherapy in ww2

Mustard gas acts as an alkylating agent in the body which damages DNA, resulting in the reduced formation of red or white blood cells and platelets; chronic exposure would affect the bone marrow and gastrointestinal tract. This causes chronic sequelae in surviving patients who might exhibit nausea, vomiting, alopecia (hair loss), or a breakdown of their immune system, increasing vulnerability to infections.


As World War II loomed closer, researchers of Allied Forces feared a repeat of mustard gas attacks. So a frantic search for an antidote commenced. In 1922, two doctors from Yale University, Louis Goodman and Alfred Gilman, while scanning through medical records of soldiers affected by mustard gas noticed many patients’ exhibited extremely low numbers of white blood cells. This prompted their attention due to white blood cells’ rapidly dividing capabilities similar to cancerous cells.


Goodman and Gilman’s initial animal trials on mice and rabbits proved successful hence they immediately started looking for a human volunteer. Eventually they found a patient known today only as J.D. with advanced lymphoma who had a massive tumor in his jaw. J.D.’s condition was considered hopeless as prior treatment with radiation no longer had any effect. He was given 10 doses of nitrogen mustard, each dosage roughly 2.5 times the standard amount today.


Within two days, his tumors shrank immensely and eventually disappeared allowing him to finally eat, swallow, and become essentially pain free. Although after a short time he relapsed and consequent treatments were no longer effective leading to his death on the 1st of December 1942, this was proof chemicals similar to nitrogen mustards could treat cancer. Further clinical trials conducted at Yale were kept a military secret until 1946, when their findings were published in The Journal of the American Medical Association.


After World War II in the UK, Professor Alexander Haddow, Director of Chester Beatty Research Institute read Goodman and Gilman’s report, providing him with the breakthrough he ever so needed.


Haddow discovered, through altering nitrogen mustard molecules, that the functionality of the molecule was dependent on the number of chlorine ions it had which he found out was two. Haddow experimented further with this finding, deciphering the molecules’ building blocks akin to tinkering with Lego and eventually found the specific molecular structure that effectively killed cancerous cells at a low toxicity; and thus pioneered the first-generation chemotherapy regimes.



How chemotherapy works

chemotherapy

Chemotherapy drugs target cells at different phases of the cell cycle by damaging the genes within the nucleus of the cell. Some drugs damage cells at the point of splitting. Some damage the cells while they're making copies of all their genes before they split. Because cancer cells tend to form new cells more rapidly than normal cells, they’re a better target for chemotherapy drugs; however, its downside is its inability to differentiate between healthy and cancer cells, leading to side effects. Even so, because cancer cells, unlike normal cells, are mutated, they don’t usually recover from chemotherapy whilst normal cells do.



Types of chemotherapy treatment

  • Chemotherapy infusions are most often given into a vein (intravenously) which is done by inserting a tube with a needle into a vein either in the patient’s arm or chest.

  • Chemotherapy pills are tablets, capsules, or liquids that are administered orally and treat most cancers, most commonly breast, colorectal cancer or leukemia.

  • Chemotherapy shots are also called intra arterial chemotherapies and are injected directly arteries most commonly in the arm

  • Chemotherapy creams are creams or gels containing chemotherapy drugs that are applied to skin to treat certain skin cancers

  • Localized Chemotherapy is chemotherapy given directly to the cancer or after it has been removed. Most commonly a thin disk wafer is placed where the cancer is or used to be where it disperses chemotherapy drugs over time as it breaks down. Chemotherapy drugs could also be directly injected into veins are arteries that feed the tumor.


Short term side effects

  • Nausea

  • Vomiting

  • Diarrhea

  • Hair loss

  • Loss of appetite

  • Fatigue

  • Fever

  • Mouth sores

  • Pain

  • Constipation

  • Easy bruising

  • Bleeding


Chronic side effects

  • Damage to lung tissue

  • Heart problems

  • Infertility

  • Kidney problems

  • Peripheral neuropathy (nerve damage)

  • Risk of a second cancer

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