A minor insight into how we develop cancer

How do we develop cancer?

The term cancer has been widely used as a generic term for a disease so devastating, that it affects not only the patient’s wellbeing but also of the patient’s social circle i.e. family and friends. Cancer is a pain the ass, no one likes cancer! But in order to treat such a debilitating disease, we have to first understand how cancer arises.

Some interesting facts about cancer incidence

Data collected in 2017 from the United States alone revealed distressing statistics of cancer in both men and women. Among the 1,688,780 estimated new cases of cancer in both men and women, approximately 600,920 or 35.6% of these cases will ultimately result in the demise of the patient. The data also disclosed an eye-opening fact about cancer – men have both a higher incidence of developing cancer and mortality rate from cancer than women. Kinda sucks to be a male isn’t it? The most prominent cancers of both men and women are prostate and breast cancer respectively. However, most cancer-related deaths are from neither of the aforementioned cancers, but instead, both genders have a significantly higher chance of succumbing to lung and bronchus cancer.

From normality to cancerous

Despite the plethora of different types of cancer afflicting humans, all of these cancers have one crucial thing in common; cancerous cells divide excessively in a non-regulated fashion resulting in the growth of tumors. Every one of the 37.2 trillion cells in a human body, have the capability and are in fact required to, duplicate its genetic material and divide into daughter cells in order to sustain life. This process is highly regulated in an ordered manner by cellular proteins termed tumor suppressers and oncogenes. Tumor suppressors are exactly as their name imply, they suppress the growth of tumors. Oncogenes, on the other hand, causes the cell to go into overdrive and divide non-stop! The normal nomenclature of an oncogene is known as proto-oncogene which simply means the normal, unmutated form of an oncogene. Any imperfection in this system and you run a risk of developing a tumor.

The hallmarks of cancer

The quintessential six hallmarks of cancer were introduced in a brilliantly written review published in Cell in 2011 by Douglas Hanahan and Robert A. Weinberg (Figure 1). For a typical human cell to be classified as cancerous, the cell must be capable of exhibiting each and every one of these hallmarks. As previously mentioned, tumor suppressors and oncogenes are responsible for the tight regulation of the processes within the cell. Unfortunately, the system is not perfect and mutations can arise in the DNA sequences of tumor suppressors and/or proto-oncogenes leading to disruptions in the normal functions of these proteins. As there are 23 pairs of chromosomes in a normal human cell, two somatic mutations in both copies of the genes are required to inactivate the function of tumor suppressors while one mutation is sufficient to enhance the activity of oncogene products. Either one of these rare events have the capability of driving a normal cell into a cancerous one.

Figure 1. The six hallmarks of cancer. Image courtesy of D. Hanahan and R. A. Weinberg (Hallmarks of Cancer: The Next Generation. Cell. March 4, 2011; 144: 646-674).

The true guardian of the genome

One of the most well studied tumor suppressor is that of p53, also known canonically as the guardian of the genome. p53 has a variety of pivotal functions in a cell which includes regulation of growth arrest during the G1/S phase of the cell cycle and also in activating proteins involved in the DNA repair mechanism upon damage by internal or external factors. The loss of function of p53 in any cell would therefore result in sustaining proliferative signaling and enabling replicative immortality, two of the hallmarks of cancer. p53 was first identified in 1979 and has since went on to be implicated in oh so many human cancers. In fact, mutations in p53 have been found in >50% of all human cancers. On top of that, p53 was even voted as the molecule of the year in 1993 by the world famous Science magazine! That is precisely the reason why many chemotherapy drugs have been developed over the years to enhance the activity of loss-of-function p53 related cancers.

Closing remarks

I have only barely scraped the surface of cancer biology but I hope to have given some of you a minor insight into this area. When we talk about cancer, it is more often than not always referred to as a war or a fight against this disease. Therefore, in order to defeat your enemy, you must first know your enemy!