Carbonizing Proton Beam Therapy for Lung Cancer
Abstract
Scientific Objective and Rationale: Lung cancers can cause death through uncontrolled local tumor growth within the chest or metastatic spread. For tumors without metastases that cannot be surgically removed, radiation therapy is administered in curative intent. However, larger tumors (i.e., stage III disease) recur in the chest in up to 50% of patients after radiation and chemotherapy, highlighting the need to identify more effective therapies. Making radiation more effective by combining it with drugs that specifically target the behavior of cancer cells may lead to improved tumor eradication. To this end, we are particularly interested to combine such drugs with particle radiation, which is different from traditional radiation (aka X-ray) treatments. Protons are available in some three dozen centers in the U.S., while carbon ion therapy is not. Protons are slightly more damaging to cells (~10%) than standard radiation, but we do not currently have any good way to amplify this difference further to make protons more effective. In contrast, carbon ions are 200-300% more effective than standard radiation. In this laboratory study, we seek to combine protons with targeted drugs that affect the packaging of DNA in cancer cells, which can potentially enhance the DNA damaging effects of protons by up to 200%. In short, we seek to carbonize proton radiation. By leveraging unique institutional resources, we will test a large number of three-dimensional lung cancer models with a collection of curated drugs (for a total of 1,000 combinations). We are hoping to produce proof-of-principle data that proton radiation can be biologically enhanced and that we can discover markers that will tell us in which lung cancers this will be possible. Area(s) of Emphasis: This research will help us understand mechanisms of resistance to radiation therapy, identify innovative strategies for the treatment of lung cancer through proton/drug combination, and potentially yield predictive markers to assist with therapeutic decision-making. Ultimate Applicability of the Research: There currently exist no anti-cancer drugs that are specifically combined with protons. Our research may ultimately lead to such combinations that can be tested in clinical trials. There is an ever-increasing number of proton centers in the U.S., so that this may become an opportunity for more patients with lung cancer. What Types of Patients Will It Help and How Will It Help Them? Proton radiation is currently mainly used and studied in patients with locally advanced (stage III) lung cancers. If our research ultimately yields novel combination therapies that can enhance the effects of protons, then local tumor eradication rates will increase and more patients will be cured of their disease. What Are the Potential Clinical Applications, Benefits, and Risks? Our basic research project will provide information that can be used for confirmation studies in the laboratory (such as animal studies) before it can then be tested in clinical trials. What Is the Projected Time Anticipated to Achieve a Clinically Relevant Outcome? We anticipate that a clinical trial based on the results of this research could be designed within 2-3 years. What Are the Likely Contributions of This Study to Advancing the Field Of Lung Cancer Research? Proton radiation has for the longest time been defined through its physical properties, which may reduce treatment side effects compared to standard radiation. However, the biological characteristics of protons have been poorly understood. If we can successfully identify novel proton/drug combinations, we may be able to reinvigorate the interest in proton radiation for lung cancer and ultimately inform novel clinical trials for patients with lung cancer. How Is the Project Relevant to Military Service Members, Veterans, and Their Families? Lung cancer remains a major problem for members of the military and Veterans, fo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210024
Entities
People
- Henning Willers
Organizations
- Massachusetts General Hospital
- United States Army