Adhesion-Dependent Regulation of Mutant K-Ras Protein Levels in Lung Cancer
Abstract
Metastatic lung cancer is the number one cause of cancer-related deaths both in men and women with around 160,000 deaths each year alone in the United States. Mutations in the oncogene K-Ras are known to drive this devastating disease. Despite all efforts to develop potential inhibitors, K-Ras remains challenging to target as a potent therapeutic treatment. K-Ras mutation status is frequently used clinically to determine patient?s prognosis, outcome and treatment. In clinical and translational cancer research, little is known about heterogeneous protein expression of mutant K-Ras in the primary tumor and how this can affect metastatic diseases. Here, we will focus on the changes of the K-Ras protein, which gives a gene its actual function, and we hope with this research we can develop in the near future new drugs and strategies to block the metastatic spread and progression of lung cancer. With this basic research approach, we hope to identify a new regulation mechanism of the K-Ras protein. We aim to interfere with this mechanism in order to stop the cancer cells to spread through the body. If we can achieve this in the time frame of this proposal, then in the long term these new insights can lead to different combinations of currently existing therapies, which given in combination would provide more benefits to the patients by making the cancer cells more vulnerable and more susceptible to the conventional cancer therapies. The study will provide important, conceptually new insights into tumor microenvironment-dependent regulation of K-Ras protein levels and how this contributes to metastatic progression. This research will improve our understanding of K-Ras protein levels in driving metastatic lung cancer. The investigation of mutant K-Ras protein levels in lung cancer can specifically help military Service members and Veterans due to the exposure to various environmental insults that are known to cause acquisition of mutations and oncogenic stress.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710182
Entities
People
- Anette Schafer
Organizations
- Massachusetts Institute of Technology
- United States Army