Written by Staff Writer Alexis Dong
Cancer has been a part of human history for millions of years.
The earliest recorded description of cancer goes back all the way to ancient Egyptian medical records from around 3000 BCE. Today, millions of people still die from this disease.
With a history that long, why have we not found the cure for cancer yet? The answer lies in both the complexity and diversity of cancer and its constantly evolving genome.
Why is Cancer so Hard to Cure?
Cancer is not just one disease, but instead a group of over 100 different diseases that involve constant changes in the genome. To better understand cancer, we must first understand an important mechanism of normal cells: the cell cycle.
The cell cycle allows the cell to divide, and is split into two parts:
- Interphase
- Mitotic (M) phase
During interphase, the cell grows and copies its DNA. This phase is split into 3 steps:
- G1 phase (cell growth)
- S phase (DNA replication)
- G2 phase (preps for cell division)
The M phase is when the newly replicated DNA is split, two different nuclei are formed, and the cell splits into two daughter cells.
There are checkpoints in the G1, G2, and M phases that only allow the cell cycle to proceed to the next phase when certain events have occurred. These checkpoints can also detect cell or DNA damage and decide whether or not to repair DNA or start apoptosis (programmed cell death).
How do Normal Cells Become Cancerous?
Many unlikely events need to happen in the same lineage of cells for cancer to form. Before a cell can become cancerous, it gets stuck at several protective barriers that prevent abnormal growth. It needs a new mutation to bypass each one. Normally, a cell must break through 4 to 7 of these defensive barriers to turn into cancer.
Therefore, tumor cells have undergone a lot of mutations. Most of the time, mutations are found at checkpoints of the cell cycle, and the cell is either destroyed or repaired before they become cancerous.
But sometimes, mutated cells find ways to avoid these checkpoints and, as a result, eventually evolve into cancerous cells. In a way, the development of tumors is similar to Darwinian evolution: each change in the DNA can lead to advantages in growth, eventually leading to a point where mutated cells form tumors.
The Genes Behind Cancer
The basis of understanding cancer has been built on top of two different types of mutations:
- Mutations that increase oncogene function
- Mutations that decrease tumor suppressor gene function
Proto-oncogenes are normal genes that work by moving the cell cycle forward and stimulating cell growth and division. When these genes mutate to gain increased function ( leading to excessive cell growth and division), they become oncogenes.
Tumor suppressor genes help slow or stop cell growth, contributing to the checkpoints found in the cell cycle.
They also activate programmed cell death in damaged cells. Decreased function in these genes can lead to uncontrollable cell growth.
A Brief History of Cancer
Looking back at the history of cancer, the earliest known written record of cancer was from 3000 BCE, found on Egyptian papyrus. Around 460-370 BCE, Greek physician Hippocrates was the first to use the term carcinos and carcinomas.
Ancient doctors believed a number of things caused cancer, for example, imbalance in body fluids or anger from the gods. With new scientific developments, many of the ancient beliefs about cancer have been disproved and/or corrected.
Giovanni Morgagni performed the first autopsies in 1761. Both these autopsy reports and the development of modern-day microscopes in the 1800s led to many fundamental discoveries about cancer. Scientists also began linking certain jobs to cancer, leading to studies in environmental factors that caused cancer.
So, How Can We Understand Cancer?
What does the progression of the understanding of cancer look like now? The current research methodology stacks layers of complexity one on top of another. Therefore, the topic of cancer and the research associated with it has become increasingly more complex over the years.
With more than 100 types of distinct cancers found in different organs, cancer becomes difficult to not only understand but also to treat. Mutated cells can use many different pathways to become cancerous. With so much variation in the disease, how can scientists across the world better understand the fundamentals of cancer?
An innovative way of understanding cancer is through a small number of underlying principles that cover the basics of this complex topic.
Genetic changes in cancer cells usually turn into these 6 essential changes:
- Being able to produce their own growth signals
- Insensitivity to growth inhibitory signals
- Evasion of apoptosis (programmed cell death)
- Limitless replicative potential
- Tissue invasion
- Metastasis
So why are these “hallmarks” so important? Being able to use these 6 principles to understand and evaluate all cancers standardizes the process of evaluating the disease and brings different scientists around the globe to a cohesive understanding.
Conclusion
The brief list of hallmarks might leave you with more questions than answers. What is different in cancer cells that allows them to make their own growth signals? How do growth inhibitory signals normally work, and why do they not work in cancer cells? How is it possible to evade cellular death? Can all cells not replicate forever? What is stopping normal cells from invading their neighbors?
We will answer all these questions in the next articles of this series.
If you learned anything, make sure to send us a message on our Instagram (@whencellsresist). We love hearing back from our readers!
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Sources:
https://my.clevelandclinic.org/health/diseases/12194-cancer
https://www.cancer.gov/about-cancer/understanding/what-is-cancer
https://www.cancer.org/cancer/understanding-cancer/history-of-cancer.html