PROSPECT: Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

Abstract

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE June 2012 REPORT TYPE SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTWe will develop a high throughput therapeutic-target focused (TTF) profiling platform and will combine this with tumor genome wide mRNA profiling and with serum or plasma profiling of phosphopeptides and DNA. We will use these molecular profiles to help define how various molecular factors alone and in combination relate to resistance to therapy, to prognosis, and to metastatic patterns at relapse. Using tumor and blood samples from non-small cell lung cancer (NSCLC) patients as well as NSCLC cell lines with defined chemotherapy resistance patterns, we will examine how molecular profiles may confer resistance and will identify new, potential therapeutic targets. The PROSPECT approach will be novel in that we will assess tumors from NSCLC patients undergoing surgical resection after having received neoadjuvant therapy as a model of resistance. Tumor surviving neoadjuvant therapy would be expected to be enriched for resistant cells. We will define what combinations of targeted therapies are most effective against resistant cell lines with similar molecular profiles, and this will drive later clinical trials (beyond the scope of this Program). Similar studies will be conducted in patients with mesotheliomas undergoing surgical resection of tumor after neoadjuvant therapy with the new Src inhibitor dasatinib. SUBJECT TERMS Provided is our 2012 FINAL report of the DOD-funded research program PROSPECT (Profiling of Resistance Patterns and Oncogenic Signaling Pathways in Evaluation of Cancer of the Thorax and INTRODUCTIONLung cancer is the leading cause of cancer death in the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Only 15% of patients diagnosed with lung cancer survive five years from diagnosis. Therapy for advanced disease ...