Tushar Desai, MD
Emerging research is investigating which cells, or subpopulations of cells, are actually capable of developing or giving rise to lung cancer.
“It is an exciting time in cancer research; there is a saying going around that ‘it is the beginning of the end of cancer,’” said Tushar Desai, MD. “It is really the ability to use these modern genetic tools to figure out the mutations and the cells, and then develop ways to target those mutations in a really personalized manner. Everyone has heard the term, ‘precision health’ or ‘personalized medicine.’ We are hopefully in a new era where we can start, one by one, to come up with good or even curative treatments for advanced cancer—for a variety of types.”
During the 2017 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, Desai, an assistant professor of medicine at Stanford Medicine, shared insight on his research in stem cells and why discovering which cells have the potential to form lung cancer is significant to the treatment paradigm.
OncLive: You discussed stem cell research at this meeting. What were the highlights of your presentation?
: My focus was on the very early stages of lung cancer development by asking, which cells are capable of forming cancer? Are all cells capable of forming cancer, or only a subset? I have been doing some work in basic lung biology, and identifying the stem cells that regenerate new cells during aging and after injury. It turns out that there are specialized subpopulations that can execute this activity and not all the lung cells can.
Our idea is that these cells, which are intrinsically better at proliferating, dividing, and generating new cells, are more easily hijacked and they can form tumors more easily than other cells. It could be that they are exclusively capable of forming tumors and that other cells can’t. So, we are doing a variety of experiments using environmental exposures to induce cancer in mice, and we are trying to mark these different cell populations beforehand and asking, “Which are the ones that are susceptible to forming cancer?”
The summary points of my talk are that not all cells in the lung are equal, in terms of their ability to generate cancer. If we can identify which ones are the most at risk, then that can help us perhaps with diagnostic treatments or trying to prevent cancer. On the flip side, if we can identify what makes the other cells not vulnerable to forming cancer, maybe we can try to figure out what they are doing to be resistant to forming cancer—in order to think about targeting those pathways for treatment of cancer.
Is this similar to the concept of chimeric antigen receptor (CAR) T-cell therapy, in which we would manipulate these stem cells for them to have changed characteristics?
Yes, I think so. It is quite likely that different cell types can give rise to the same kind of cancer. For example, there is lung adenocarcinoma. If it came from 1 type of lung cell versus another—if you just look at the histology—they both look like adenocarcinoma. However, if you can figure out that they came initially from a different cell site, then you can try to ask what intrinsic capacity does the 1 cell type have versus the other. And, you can think of treatments to target those special abilities.
Therefore, it is looking at what the mutation does, and how the mutation makes the cell divide. It is sort of saying, “Okay, what is this cell naturally capable of doing?” as well as targeting those pathways, which are different than in another cell. It could also be that if they generated from a different cell site they could express different markers, so it’s possible you could target those markers using some sort of antibody-mediated treatment to eradicate them. Those are the kinds of things.