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Lung Cancer Research Program - About the Program

Lung cancer is the most deadly cancer worldwide and kills more people than other top three cancer types (breast, prostate, and colon cancers) combined. It becomes a devastating public health hazard and challenges the nation to find a cure for the disease.

Over the past decade, increased public interest in health care has influenced the funding of scientific research. From fiscal year 1995 (FY95) to FY05, Congress has directed the Department of Defense (DOD) to manage numerous targeted research initiatives. As the manager for these initiatives, the U.S. Army Medical Research and Materiel Command’s (USAMRMC’s) Office of the Congressionally Directed Medical Research Programs (CDMRP) has executed over 40 research programs. The goal of CDMRP in managing these programs is to fund scientifically meritorious research that addresses the topic areas specified by Congress.

From FY01 to 05, the DOD has funded lung cancer research to the University of Texas M. D. Anderson Cancer Center to explore multiple avenues of research, prevention, diagnosis, and therapy that would yield new prevention and treatment options for lung cancer.

Under the leadership of Dr. Waun Ki Hong, Principal Investigator of the Lung Cancer Research Program at the M.D. Anderson Cancer Center, we have developed five research grants over the five years. Our ultimate goal is to reduce morbidity and mortality through early detection, prevention, and treatments. The five research grants are highlighted as below.

The BESCT (Biology, Education, Screening, Chemoprevention, and Treatment) program developed in 2001 for five years aims to develop effective therapeutic and preventive strategies targeting smokers and lung cancer patients by defining the molecular processes contributing to lung cancer development and progression to recognize genetic and phenotypic changes early enough to be reversed with molecular targeted therapy. Specific goals of this program are to understand molecular alterations in lung cancer, develop lung cancer prevention strategies, and implement experimental molecular approaches to lung cancer.

The TARGET (Translational Approaches for the Reversal, Genetic Evaluation and Treatment of Lung Cancer) program initiated in 2002 for three years aims to understand the biology and therapy of lung cancer in the settings including cell lines, animal models and human subjects. Specifically, the program proposed ten research projects designed to understand the epidemiology, molecular biology, genetics and epigenetics of lung cancer in the context of tobacco-damaged aerodigestive tract tissue, and anti-tumor activities of some promising agents, and to develop improved pulmonary gene delivery approaches and orthotopic murine human lung cancer model to test effects of antiangiogenesis agents.

The VITAL (Vanguard Trial of Investigational Therapeutics in Adjuvant Treatment of Lung Cancer) program developed in 2003 for five years is to develop a risk assessment model for lung cancer recurrence and development of smoking-related second primary tumors based on the understanding of the biology of lung cancer development in the high-risk population. Also the program will identify the most effective combination of agents in early prevention in the high-risk population.

The IMPACT (Imaging and Molecular Markers for Patients with Lung cancer: Approaches with Molecular Targets, Complementary, Innovative and Therapeutic Modalities) program granted in 2004 for four years addresses the lung cancer as a heterogenous disease that requires a coordinated attack on multiple altered signal pathways in a truly integrated fashion. Therefore the program targets several key pathways for their therapeutic potentials alone or in combination with each other or with radiotherapy, explore applications of molecular imaging for targeted therapy, identify targeted peptides for systemic delivery of therapeutic and imaging agents, and discover new molecular abnormalities in lung cancer. The developmental research projects explore new areas in treatment of malignant pleural effusion with targeted agents and in education of teens and young adults for smoking and resultant lung cancer occurrence.

The BATTLE (Biomarker - Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) program developed in 2005 for four years seeks to establish individualized targeted therapy by prospectively examining patient’s tumor biomarker profiles and assigning them to corresponding targeted therapies with the expectation to yield a better clinical outcomes. The overall goal is to provide a strong, rationale-based targeted treatment strategy through a program that capitalizes on our rich understanding of lung cancer biology, our capability to develop and analyze biomarkers, our experience with clinical trial implementation and enrollment of large numbers of patients with advanced non-small cell lung cancer, and the availability of several agents that target the critical signaling pathways in lung cancer. This novel approach will be a proof-of-principle experiment to test the benefit of molecular-based individualized targeted therapy for lung cancer patients.

The PROSPECT (Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification) developed in 2006 for four years propose to systematically investigate via novel molecular profiling methods the mechanisms of therapeutic resistance and to develop rational therapeutic strategies for overcoming this resistance. Specifically, we will 1) investigate mechanisms of chemotherapy resistance through the analysis of tumors that are resected after neoadjuvant chemotherapy and thus enriched for resistant cells; 2) apply a novel therapeutic target-focused (TTF) molecular profiling platform in the systematic evaluation of potential treatment targets for chemotherapy-resistant non-small cell lung cancer (NSCLC), and quantitatively assess the effects of treatment on key signaling pathways; 3) investigate the molecular profiles of NSCLC tumors from patients with sensitivity, primary resistance, or acquired resistance to chemotherapy and identify patterns of treatment failure; 4) develop a model based on molecular profiling that will predict the effects of targeted treatment on chemoresistant tumors including NSCLC and mesothelioma; 5) assess how molecular profiles that predict sensitivity to therapy impact on prognosis in untreated patients.