Exploring the Link Between Lung Cancer Lineage Heterogeneity and Microenvironment
Abstract
Scientific Objective and Rationale: The recent advent of precision medicine and immunotherapy has improved the quality and length of patients’ lives. Still, the prediction is imperfect, and despite initial response to the treatment, cancers eventually come back and kill the patients. Therefore, it is critical to understand the ecology of this complex disease. Lung cancer typically consists of diverse populations of cancer cells, which resemble various types of normal lung cells. Cancer cells usually retain their original cell functions to maintain the balance and ability to communicate with surrounding cells. Lung tumors consist also of immune and stromal cells. The current immunotherapy is founded on the principle that interfering with the communication between cancer cells and immune cells helps the immune system to reengage. While this is an exciting moment, there is much to be improved upon, including how we predict who will benefit from it and the efficacy on those who do not. It is clear that we need better understanding on both sides of the communication. By looking at the features that show how the genomes of cells are organized and are different in every cell type; our group can now classify cancer cells by their identity as lung cells. This study focuses on the identity of cancer cells and how those characteristics will affect our immune system and be influenced by it and ultimately contribute to formation of lung cancer. We hope that results will lead to a strategy to manipulate cell identity of lung cancers and their interactions with immune and stromal cells. The proposed study is in alignment with the Lung Cancer Research Program’s Area of Emphasis to “understand the molecular mechanisms of initiation and progression to clinically significant lung cancer.” Career Goals in Lung Cancer Research: Since the completion of my clinical training in pulmonology, where I cared for many patients confronting lung cancer, my research career has been entirely dedicated to the research on this devastating disease. As a trainee, I have pioneered the field of regulations of cell identity in certain subsets of lung cancers while establishing my expertise in cancer genome analyses. Now my scientific goal is to extend this understanding to all subsets of lung cancers and to thoroughly disentangle the complexity and diversity of underlying programs at individual cells comprising lung cancer, with a further goal to advance such knowledge into a tractable path for clinical utility. This award would afford me time to prove this novel concept and eventually fully utilize our large amount of new genomic information and immunologic features that had not been available; provide me with an opportunity to hone my skills to develop novel technologies; and build necessary partnerships to complement my skillset. Ultimate Applicability of the Research: The proposed study seeks to identify different subclasses of lung cancers that may interact with their surrounding neighbor cells and to understand the precise mechanism of how such interactions are operated. It further aims to understand how dynamic changes at the population level within a tumor can occur during the course of cancer development and response to treatment. Historically, the very concept to exploit malignant cells’ reliance on cell identity programs for their survival and communication with surrounding cells as therapeutic strategy has been successfully used in blood cancers such as acute myelogenous leukemia. However, this has not been fully explored in the field of non-blood cancers. By taking advantage of our current ability to utilize new genome technologies, we seek to establish fundamental information about such programs that can distinguish different subclasses of lung cancers and how they interact with surrounding cells. Our approach will test the utility and biological importance of information gained through our genomic analyses regarding how ea
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910613
Entities
People
- Hideo Watanabe
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army