Thanks to your continued support,
Mezin-Koats Colon Cancer Research has funded its first project at the Masonic Cancer Center, University of Minnesota
Developing personalized, targeted therapy for colorectal cancer patients
An exciting new era of personalized, targeted cancer therapy is starting to be practiced in the clinical setting for cancer patients. The basic steps in this treatment strategy are to biopsy the patient's tumor, perform genetic analysis on the tissue sample, and then prescribe drugs that counteract the specific genetic changes identified in the cancer. Unfortunately, there are several roadblocks currently preventing the increased use of personalized cancer therapy in colorectal cancer patients. First, although a few of the key genetic changes that contribute to causing colorectal cancer are known, the majority of genetic changes that cause colorectal cancer are still undefined. A typical tumor in a colon cancer patient contains about 80 different mutated genes, but currently, there isn’t certainty as to which of these 80 genes actually caused the cancer. Without knowing the specific mutations that contributed to the cancer it will be difficult to choose the correct targeted therapy. Second, although there are dozens of targeted therapies being developed by pharmaceutical companies, it is currently extremely difficult to test these drugs in clinical trials, especially in combinations.
The Masonic Cancer Center, University of Minnesota research program aims to overcome these two major roadblocks. First, they have developed mouse models that can identify which genetic changes directly lead to intestinal cancer. Their model uses a "jumping gene", called the Sleeping Beauty transposon, to randomly mutate genes. They can then identify the specific mutated genes that cause intestinal cancer. From this project they have identified over 100 new candidate cancer genes. The second step of the research program is to test these candidate cancer genes, both singly and in combination, to discover which genes work together to cause colon cancer. Once they have identified the combinations of mutations that can cause cancer, they will create these mutations de novo in cells, transplant these cells into mice and create genetically defined cancers in mice. Next, they can use these mice to test various combinations of targeted therapies to find out which combinations are effective and what are the appropriate dosages. The ultimate goal is to use this information to initiate clinical trials in humans based on their findings.
Our project aims to create these genetically defined mouse tumors. The Masonic Cancer Center, University of Minnesota already has its list of known and suspected genes that can cause colorectal cancer and they are developing methods of generating these mutations in combinations of two to five different genes per cell. They are engineering these genetic changes into a mouse cell line that can be transplanted back into a mouse to generate colon cancer. In the past, the vast majority of experiments similar to theirs used human cells transplanted into mice that did not have an immune system. Unfortunately, the results from these experiments frequently did not recapitulate what happens in humans because the mouse model did not have an immune system. We believe the University of Minnesota’s method is superior because it uses mouse intestinal cells transplanted into a mouse with an intact immune system. The Masonic Cancer Center, University of Minnesota recently acquired the first mouse colonoscopy machine in Minnesota. This technology will allow them to directly deliver their engineered cancer cells to the colon and monitor the growth of the tumors over time. Once they have perfected the method of grafting the cancer cells into the colon, they will use the mice in preclinical trials, testing various combinations of targeted therapies to treat the cancers.
Update: January 2016
We have been moving forward with our project to test combinations of genetic causes of cancer in cell lines in our laboratory. We are testing genes that we discovered as drivers of colorectal cancer. Other colon cancer projects in our lab that are not directly funded by the Mezin-Koats money include analysis of the Cystic Fibrosis gene, CFTR, and two other genes, WAC and TM9SF2, which we suspect are drivers of colon cancer. As always, the goal is to find new treatment targets and better ways to treat colon cancer.