HealthySteemian: Cancer, Causes and development of anticancer drugs

Cancer is a general term used to describe all diseases associated with aberrant cell growth or division. Neoplasm is the medical term for cancer. It is referred to as neoplastic disease and anticancer drugs are referred to as neoplastic agents.
Cancer is a fall out of a disruption in the balance between cell production on one hand and cell loss or destruction on the other hand that is the Homeostatic mechanism/balance between cell production and destruction in the body.
In cancer, there is an increase in the rate of cell production and decrease in the rate of cell loss such that it is skewed in favour of cell birth/production. In this case homeostatic balance between cell production and cell destruction is lost or evaded by cancer cells leading to continuous replication of cancer cell lines.

Types of cancer treatment

Cancer is treated via three (3) main approaches.
1. Surgical treatment: excision of cancer by surgical operation. It is the most effective detected early when cancer has not metastasised.
2. Radiotherapy: treatment with radiation is usually used if cancer is easily accessible and hasn’t metastasised.
3. Chemotherapy: this is the use of chemical agents to selectively destroy cancerous cells while sparing the normal uninfected cells. This therapy is advantageous when cancer has metastasised because it can be used systemically.

Pardon Me:
As a Chemistry student most of my write up on this topic would be so much inclined towards the use of chemistry jargons; though I would try to write to everyone’s understanding as much as I can. Thus my Delve into cancer chemotherapy begins:

Approaches used for cancer chemotherapeutic agents' discovery

There are three (3) main approaches to discovery of cancer chemotherapeutic agents
1. Cytotoxic/cytostatic approach: This involves directly killing the cancer cells by directly interfering with cell division processes. Agents used here are called cytotoxic/cytostatic agents. This approach is used up till date. Both synthetic (laboratory prepared) and natural cytotoxic agents exist. This approach is also called the classical approach.
The drugs that act using this approach interferes with either of the two activity phases of the cell cycle.
a. DNA Synthesis Phase (S-Phase)
b. Mitosis Phase (M-Phase)
The two phases are separated from each other by two resting phases called G1 and G2 phase.

The G1 is in dynamic equilibrium with the long term resting phase G0. When G1 goes to G0 phase, the cell is not dividing at all. It is called the inactive phase.
Cytotoxic agent do not affect cells in G0 phase but rather on either the G1 or G2 phase where the cells are actively dividing.
Cytotoxic agents generally inflict DNA damage, these agents are generally toxic to normal cells because there is no difference between cancerous cells and normal cells regarding cell division. The only difference being capitalised (using these agents) is not a structural difference but a quantitative difference because cancerous cells are rapidly dividing. There are still normal cells that are rapidly dividing like cancer cells examples are GIT cells; bone marrow cells and cells that generate hair follicles. This means that cytotoxic agents would affect these normal cells and cause things like Agranulocytosis / bone marrow suppression, loss of hair (alopecia) and Gut Ulcer. Suppression of bone marrow would lead to lower White Blood Cells (WBC) growth thus lowering immunity which would leave patient open to opportunistic infections like Tuberculosis.
2. Targeted approach: This involves killing cancer cells by interfering with biochemical processes other than cell division. Drugs in this category are not yet in clinics and they could be less toxic than cytotoxic approach.
There are some biochemical mechanisms or processes that are crucial to the establishment of cancer and its metastasis; it is believed that if such mechanism/processes are inhibited then cancer can stop or be destroyed. For example some enzymes called Kinases are crucial for normal cell growth and cancer proliferation, it is believed that if these enzymes can be inhibited then cancer can be checked. There are also enzymes known as Proteases found to be crucial to metastasis of cancer, it is believed that if there are Protease Inhibitors as anticancer agents then cancer can be checked. Another line of thought for discovering targeted chemotherapeutic agents could be towards inhibiting Angiogenesis (Synthesis of Blood Vessels), however this would be cytostatic rather than cytotoxic.
3. Immuno-stimulation/Immuno-stimulatory approach: This involves boosting Immune system to kill cancer cells. The idea has been there since 1960’s but drugs in this category are yet to be in clinics. There are evidence to believe that cancer is instituted when the immune response has been compromised. Therefore boosting the immune system would be a rational approach to cancer chemotherapy.

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In Drug discovery there two main stages
1. Lead (molecule) discovery
2. Lead modification (Design Stage)
Drug lead is any molecule of bioactive interest. The lead has potential to perform therapeutic activity but not optimum, it may be toxic thus needing modification. One of the major type of cytotoxic agent in a category known as Alkylators was discovered during the First World War whose lead molecule is Sulphur mustard (now used as template for anticancer drug discovery). Sulphur mustard was first used to kill people during this war. It was later discovered that bodies of soldiers killed with sulphur mustard had gastric ulcerations, bone marrow aplasia and low WBC when thoroughly examined. This suggested that sulphur mustard had profound effect on inhibiting rapidly dividing cells thus a template for anticancer drug discovery was formed. Scientists thought of attenuating Sulphur mustard by removing sulphur and replacing with nitrogen (Isosteric Exchange).
Further modification of this template led to discovery of Mechlorethamine and Chlorambucil still of clinic use till date.
This shows that drug discovery can be achieved by observing side effects of existing drugs.

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My personal believe is that one of the causes of cell abnormalities such as cancer are oxidative stress, compromised immune system and slow cell detoxification resulting from harmful environmental pollution that the body inhales, absorbs or digest.

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Pheww! I have to stop here quite a lengthy one for me, trust me I tried to skip a lot of details and chemistry jargons. Hope this was helpful. Stay tuned for next HealthySteemian post on Oxidative stress and its implications.

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I am grateful to have been tutored by Dr. Ajala of the Pharmaceutical Chemistry Department of the University of Lagos who imparted this knowledge shared here.

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Stay Healthy steemians!

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