Using CRISPR to investigate pancreatic cancer

Writing about pancreatic cancer always gives me a pang. My grandmother died from the disease over 30 years ago, but I still remember the anguish of her diagnosis and the years of chemotherapy and surgery she endured before her death. This disease is much more personal to me than many I cover.

Unfortunately, survival rates haven’t really budged since I was in high school, in part because the disease is often not diagnosed until it’s well established. As geneticist  Monte Winslow, PhD, described to me in an email:

Pancreatic cancer is very common and almost uniformly fatal. Human pancreatic cancers usually have many mutations in many different genes but we know very little about how most of them drive pancreatic cancer initiation, development, and progression. Recreating these cancer-causing mutations in cells of the mouse pancreas can generate tumors that look and behave very similarly to human pancreas cancer.

Unfortunately, traditional methods used to generate mouse models of human cancer are very time-consuming and costly.

Winslow, along with postdoctoral scholar Shin-Heng Chiou, PhD, and graduate student Ian Winters, turned to the latest darling of the biochemistry world — the gene-editing system known as CRISPR — to devise a way to quickly and efficiently turn off genes implicated in the development of pancreatic cancer in laboratory mice. Their work will be featured on the cover of Genes and Development on Monday. As Winslow described:

Our goal was use CRISPR/Cas9 genome editing to make altering a gene of interest in pancreas cancer simple and fast. Shin-Heng and Ian worked together to develop novel tools and bring them together to generate this new system that we hope will dramatically accelerate our understanding of pancreas cancer. The increased basic understanding of how this cancer works may ultimately lead to better therapies for patients.

We’ve written about CRISPR here  before and The New York Times published an excellent article about the promise of the technique. Now it’s coming into its own as a way to generate new animal models of disease.

Winslow and his colleagues plan to use their approach to investigate not just the genetic mutations involved in the development of pancreatic cancer, but also those responsible for its progression and metastasis. I’m eager to see the results of their subsequent research, and wish I could share them with my grandmother. But Winslow and his colleagues are not alone in their push to better understand this deadly disease. As Winslow explained:

There are a growing number of research efforts focusing on pancreatic cancer, which is projected to become the second-leading cause of cancer-related deaths in the United States.  It is about time that this cancer type starts getting the attention it deserves. We are happy to be part of a growing pancreatic cancer research community at Stanford that includes both clinical and basic science researchers.

http://scopeblog.stanford.edu/2015/07/23/using-crispr-to-investigate-pancreatic-cancer/