Monte Winslow, PhD
Academic researchers are hoping that their efforts on the gene-editing technology of CRISPR (clustered regularly interspaced short palindromic repeats) will lead to the ability of turning off mutated genes in patients with a variety of malignancies, including lung cancer.
CRISPR technology allows for editing or alteration of a cell’s genome, and inactivating or repairing genes as needed by changing the DNA sequences.
In the lab, researchers are currently exploring the diversity of various tumor genotypes in mouse models to learn more about cancer biology and exactly how mutated genes impact lung cancer progression, according to Monte Winslow, PhD, assistant professor, Department of Genetics and Department of Pathology at Stanford Medicine. Moreover, he adds, they are exploring mutated genes to determine which ones are associated with drug sensitivity.
In an interview with Winslow during the 2017 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, he shared the work on CRISPR being developed in his lab, and how this technology might help advance treatment for the non-driver NSCLC population.
OncLive: What did you highlight regarding CRISPR technology in your presentation?
The main thing that we are interested in doing is developing model systems where we can generate many different types of tumors in mouse models. These are very important cancer genes. Can we create mouse models of human cancer? We have a diversity of different genes mutated. We are looking at the diversity of different genotypes of tumors in individual mice so we can first learn about the biology of how these genes being mutated impacts cancer development, or cancer progression, in the lung.
Secondly, we want to use these models to understand if there are certain genes, when mutated, in the human disease that might lead to sensitivity to different therapies. These might be therapies that are already FDA approved for other cancer types, but we don’t know if there are some rare genotypes of tumors that are going to be exceptional responders to these sorts of drugs. It helps that these platforms we are developing can help prioritize to get to patients with the right genotypes of tumors.
What is the history of CRISPR?
It is a very interesting history of CRISPR; it is originally from various model organ systems where they discovered it. Then, it’s applied now to this genome engineering, where it’s quite easy to engineer these components to create breaks in the DNA. Those breaks can be repaired in a way where the gene is now inactivated.
So, as far as the cancer modeling side, what we have been involved in is trying to harness this CRISPR system to be able to inactivate genes in these sort of cancer models. Other people have also contributed to this field, so that has been a real advance. Before being able to do these things, it would really take years or longer to look at a function of any individual gene in a cancer model. Now, we can look at tens of genes in the same amount of time, and that has really been a huge advance. Our hope now is to do more of that— more efficient, quantitative ways and then start applying these question of looking for different drug sensitivities, which is a very open question. Lots of people are interested in it.