Date: November 7, 2022.
Happy, a girl whom I knew as someone who is always . . . yes, just like her name suggests, happy, always spreading radiant smiles with selfless acts of kindness. Of course, everyone has their own share of despair in this world, and she had her own too, but she always carried an optimistic frame of mind. Something very peculiar about her was that she could find joy in the simplest and littlest things. For instance, a clear blue sky with fluffy clouds, a gradient sun at the time of sunset, bright green grass, flowers, chirping birds, a night sky full of stars, a moon in all its phases, randomly exchanging soft smiles with strangers, making her friends and family laugh, and a lot of such ordinary things used to make her happy. You could often find her smiling by herself, remembering these simple things. But then something happened one day, and all of a sudden, maintaining her optimism became the toughest task. She was diagnosed with breast cancer.
Just like happy, cancer randomly strikes millions of people around the world every year and devastates their lives, physically, mentally, and financially, in every way possible. There has been no cure for it for centuries, and it is still the leading cause of death worldwide.
Let us first understand, What is Cancer?
As we grow, our body size increases. . . when we get injured, the wound heals within a few days. Ever questioned how?
Well, the cells in our body undergo a series of events where they grow and divide into two cells. This series is called the cell cycle and the process of cell division is known as mitosis. Now, of course, prior to division, every cell undergoes a growth phase, where it increases in size. This phase is known as the G1 stage. Then, like good parents, your cells make copies of their DNA, so that each daughter cell gets an equal number of chromosomes (DNA carrying thread-like structures). This phase is known as the S stage. In the subsequent stage, G2, the cell prepares to undergo division, mitosis, in which the copied DNA is divided between two daughter cells.
These two daughter cells have two fates: either to enter the resting state, Go (they can either permanently stay here or restart the cell division cycle based on certain signals) or to re-enter the cell cycle and undergo division, as in the case of embryo development and tumors.
The cell cycle is a continuous series. However, things could go wrong at any moment, so we have specific checkpoints (at G1, G2 and M stage) to ensure that nothing goes wrong. Proteins called cyclins and CDKs are the main drivers of the cell cycle. When a cell wants to enter the cycle, it will start producing these proteins. Cell progression is regulated by the complex of different CDKs and cyclins. In G1 phase, CDK4/6 forms a complex with cyclin D, driving the cell into S phase. Here, CDK1/2 forms a complex with cyclin A. This further drives it into the G2 phase, where CDK1 and cyclin E form a complex and the cell undergoes mitosis. Now, if the levels of CDKs and cyclins rise above a certain level, cells will continue to enter the cell cycle and proliferate uncontrollably (resulting in the formation of a tumor). This is one of the mechanisms of cancer.
But how does the level of CDKs and cyclins rise? Answer, genetic mutations. Often, cells detect mutations and either correct them or program self-destruction (apoptosis) in them. However, some mutations enable cancer cells to proceed unchecked through the cell cycle. These mutations include:
1. Point mutations: a single nucleotide base (A/ T/ G/ C/ U) is changed.
2. DNA amplification: an increase in the number of a certain gene.
3. Chromosomal rearrangement: changes in the structure of the original chromosome.
4. Epigenetic modifications: chemical reactions and structural modifications (DNA methylation and histone modifications).
These mutations have two major effects: either they activate onco genes (mutated genes that can potentially cause cancer) such as Ras and Myc, or they inactivate tumor suppressor genes (genes that prevent tumor growth and cell proliferation) like p53, APCs, and BRCA 1/2.
You might be wondering, if cancer is an uncontrollably growing tumor, we could just surgically remove it and voila! Cured! Well. . . no. . .
Cancer tumors are malignant. They are non-capsulated, unbounded, can invade tissues and produce chemicals that cause the surrounding blood vessels to grow, which gives them a massive blood supply to feed on. Moreover, they can metastasize, that is, they can spread to different parts of the body, which is extremely fatal.
When normal cells change into cancerous cells due to genetic mutations, they cause abnormal changes in the tissue (dysplasia). One of the most significant points to bear in mind is that a single mutant cell gives rise to a tumor (neoplasia), which develops and gains more mutations over time. These modifications result in more subpopulations, and each of these subpopulations has the capacity to divide and undergo further mutations. This is known as clonal heterogeneity (clonal = duplicate; heterogeneity = diversification). Consequently, treatment becomes incredibly difficult, since a drug that affects one tumor cannot possibly affect other tumor subpopulations.
Every cell, every patient, and every cancer is different.
As discussed above, the tumor produces chemicals that cause the formation of new blood vessels (angiogenesis). This allows cancer cells to enter the blood stream easily, where they interact with immune cells. But because there are so many of them, they vanquish the immune system and infiltrate more tissues and organs. Additionally, they suppress the immune system, which prevents it from recognizing and destroying cancerous cells.
Furthermore, cancer stem cells (CSCs) are a serious threat in addition to clonal heterogeneity. Normally, stem cells are those that have the capacity to divide and produce every organ in your body. They have the ability to regenerate, replace, repair, and restore cells. Similarly, a cancer stem cell has the ability to multiply and create cancerous cells resulting in malignant tumors. As conventional cancer therapies target only rapidly dividing cells, these CSCs are spared, making them resistant to chemotherapy and radiation. Moreover, they significantly contribute to tumor angiogenesis which results in their development and maintenance. At the end of a normal cancer treatment, where you are clinically diagnosed as cured, a single undetected residual CSC could lead to a potential future relapse.
Cancer is a serious, tormenting, ruinous, despairing disease, which usually puts its bearer to eternal rest.
Do you think this heart-rending condition can bring humanity’s hopes to an end? No.
Over all these years, our absurd audacity to never accept failure and to keep getting up again and again, when we are defeated, has significantly increased cancer-survival rates across the globe. The very things that once imposed harm, are now harnessed and providing treatments. For instance, the lethal mustard gas, which was horribly used during World War II, later led to the origin of The Cancer Chemotherapy. Over the past few decades, cancer treatments have transformed dramatically, enticing us to hope that one day, we’ll be able to cure it. In future blogs, I will shed light upon the treatment marvels that we have discovered and developed to get rid of this agonizing dementor.
Meanwhile, live like happy; spread radiant smiles with selfless acts of kindness and carry an optimistic frame of mind :)
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