Development of a Novel Platform for In Vivo Delivery of Antagomirs to Study Cetuximab Resistance in Colorectal Cancer
Abstract
Colorectal cancer is the third most commonly diagnosed type of cancer in Veterans and the general public, and it is also the third leading cause of cancer-related death. Recently, improvements in widespread screening have decreased the number of people who die from this disease due to early detection. However, advanced colorectal cancer is still very lethal. Those who are diagnosed with advanced colorectal cancer still generally die from the disease, and for that reason new therapeutic approaches are still needed. One very promising Food and Drug Administration (FDA)-approved drug for individuals with advanced colorectal cancer is called cetuximab, and 12% to 17% of patients receiving cetuximab have long-lasting responses. Furthermore, up to 72% of patients may benefit from cetuximab when it is combined with other types of chemotherapy. Unfortunately, it is quite common for patients receiving cetuximab to become resistant to the drug, allowing their cancers to continue to progress. It is currently unclear how and why this happens, and there is a significant need to study this further in order to overcome the problem. Dr. Coffey recently found one approach that colorectal cancers use to become resistant to cetuximab. This tactic relies on something called epigenetics, which is related to how cancer cells read our genetic code rather than how genetic code itself might be changed. However, it is unclear exactly how the colorectal cancer cells use this particular tactic to become resistant to cetuximab, and we need to develop new tools to study this problem. Fortunately, the tools we will develop may be used to study epigenetics in other types of cancer in the future. Dr. Houghton, the Principal Investigator (PI) has been working in cancer research for over 6 years, and his previous work in pancreatic cancer has led to multiple trials. He joined Vanderbilt University Medical Center in 2016 as an Assistant Professor with the goal of developing novel approaches to studying and treating cancer, particularly cancers that are difficult to treat like advanced colorectal cancer. In particular, he aims to use his background in organic chemistry and cancer imaging to develop tools to answer complicated questions about how colorectal cancer becomes resistant to cetuximab. This award will provide the resources that Dr. Houghton and his laboratory need in order to develop and implement new tools to study the causes of cetuximab resistance. Importantly, this award will allow him to work under the guidance of a world-renowned leader in colorectal cancer research, Dr. Robert Coffey (Career Guide). In addition to scientific collaboration and guidance, Dr. Coffey will act as a mentor to Dr. Houghton as he seeks to establish himself as a leader in the field of colorectal cancer research. In particular, Dr. Coffey will provide guidance in preparing grants for future funding, how to manage his laboratory and personnel, and he will also help Dr. Houghton establish a professional network of experts in the field. Ultimately, the goal of this project is to develop tools that we use to increase our understanding of how some colorectal cancers become resistant to cetuximab through epigenetics. We will use the information we gather using our new tools to generate hypotheses about the causes of cetuximab resistance in colorectal cancer. By improving our understanding of these tumors at the epigenetic level, we can design new treatment strategies to overcome this type of resistance. In doing so, those diagnosed with advanced colorectal cancer who do not benefit from cetuximab treatment, or develop a resistance after being treated, will have a better chance of survival. There are many types of chemotherapy drugs that are already approved, and we may be able to identify which of those drugs could help patients when cetuximab fails or we could potentially identify which drugs would restore sensitivity to cetuximab. In this case, the benefit to patie
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910446
Entities
People
- Jacob Houghton
Organizations
- United States Army
- Vanderbilt University