Lung cancer is one of the largest contributors to cancer-related deaths in the world. The reason why lung cancers have a high chance of causing deaths is due to the property of cancerous cells or tumors called plasticity.
It is the cells ability to shift forms so that they can avoid the impact of certain medicines. Scientists were aware of such a possibility but had no evidence to prove it.
But all that changed when Dr. Purushothama Rao Tata and his team at Duke University School of Medicine closely examined the tumorous cells and their properties. Upon careful evaluation, Tata and the team of researchers made a breakthrough in how we perceive cancerous cells.
They found that the tumorous cells hid a tiny stomach, small intestine, and duodenum inside them. This was a baffling discovery as these cells on the lungs were showing the structure of cells found in human stomach and intestines.
To introduce some clarity, one must understand that cells at different parts of the human body have a different shape, size, and properties. So the cells present in the lungs are not same as those present in the stomach.
Tumors are a cluster of cells that do not look similar or provide any use to the body. But finding that tumor cells were comprised of cells that are present in other parts of the body is a remarkable discovery.
How Tumors Are Created and How Genes Come Into Play
All the cells start out as same, certain genes present in the cells change their form as well as functions. So different parts of the body is a result of cells that have certain genes.
The gene that is responsible for cells to take the form of lung cells is a compound called NKX2-1. When researchers examined the tumorous cells, they found out that these cells didn’t have the NKX2-1 gene in them.
With a dominant gene controlling the growth pattern of the cell, the cell begins to mimic the next most predominant gene. So these tumors began to develop into other forms of cells.
Hence, when chemotherapy is applied to these cells, the chemicals won’t have any effect on them (plasticity) as the cells have taken a different form and the chemicals aren’t designed to target such cells.
It cannot be summed up better than the words of Prof. Purushothama Rao Tata himself, "Cancer cells will do whatever it takes to survive."
To test their new findings, the researchers experimented with mice as they eliminated the NKX2-1 in their lungs. It then showed that their lung cells started to change and began producing digestive enzymes.
In the next set of experiments, they eliminated the NKX2-1 genes from the lung cells and activated the oncogenes KRAS and SOX2. It resulted in the development of tumors that resembled cells from midgut and hindgut.
The team developed a "mini-lung tumoroid" system – a miniature version of the lung tumor tissue to find that altering the genetics was enough for the lung cells to form tumors.
"Cancer biologists have long suspected that cancer cells could shape shift in order to evade chemotherapy and acquire resistance, but they didn't know the mechanisms behind such plasticity," Tata mentioned.
"Now that we know what we are dealing with in these tumors – we can think ahead to the possible paths these cells might take and design therapies to block them."
In future, Tata wants to apply his novel mini-lung tumoroid system to further identify possible mechanisms that promote resistance in lung cancer cells.