Dual Targeting of Tumor-Initiating Cells in Small Cell Lung Cancer
Abstract
Lung cancer is the leading cause of cancer deaths, with small-cell lung cancer (SCLC) representing the most aggressive subtype. Resistance to chemotherapy is a major obstacle to successful treatment of SCLC, and poor survival is due to a lack of progress in treatment strategies. Therefore, the lack of specific treatment options for patients with SCLC necessitates the discovery of new, rational therapies for this important subtype of lung cancer. Sub-populations of tumor-initiating cells (TICs) are thought to be major drivers of drug resistance and relapse that make SCLC such a difficult cancer to control. Our studies will test two entirely novel therapeutic approaches, providing data to support translation into the clinic. Rova-T and CBL0137 are two novel agents that preferentially kill TICs. Here, we will test the idea that combinations of TIC-targeting drugs will kill TICs more completely than single drugs, preventing tumor recurrence. We propose to combine these two drugs with the current standard-of-care chemotherapy, which mainly kills bulk tumor cells, as a novel method to induce a more prolonged inhibition of tumor growth. Successful completion of the proposed studies will allow us to address our mission by laying the groundwork for implementation of novel therapeutic strategies to improve and save lives of SCLC patients in the near future. According to the American Lung Association, about 30% of active duty military personnel smoke, and because many have a hard time quitting, this suggests that smoking-related diseases such as lung cancer will remain a health issue for Veterans long into the future. The specific lung cancer studied in this proposal, SCLC, is the most closely tied to patient smoking history among all types of lung cancer and deserves more intense research effort because of its high lethality. Collectively, these facts strongly argue that research directed at improving SCLC treatment outcomes will improve the long-term health of Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810632
Entities
People
- Sarmishtha De
Organizations
- Cleveland Clinic
- United States Army