Non Invasive Treatment Response Monitoring and molecular characterization of NSCLC using Cell-free DNA isolated by an AC Electrokinetic Device

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DESCRIPTION (provided by applicant): Our overall goal is to commercialize a cost effective, rapid, point-of-care, treatment response monitoring system that can identify non-responding patients with non-small cell lung cancer (NSCLC) that would be vital to doctors who determine the course of therapy. In this Phase I proposal, we will demonstrate that an inexpensive prototype AC electrokinetic (ACE) Chip developed at Biological Dynamics, Inc. can effectively isolate cell-free circulating DNA directly from plasma rapidly, and establish the proof of concept for using CFC DNA quantitation as a molecular signature for treatment response monitoring (TRM). Lung Cancer is the most common human adult cancer in terms of both incidence and mortality. In 2008, there were 1.61 million new cases, and 1.38 million deaths due to lung cancer worldwide. Prognosis is generally very poor: of all people with lung cancer, only 15% survive for five years after diagnosis. The standard method of monitoring of response to therapy is serial imaging done every 2-3 months. In the research setting, RECIST criteria are used to define progression, but in the regular practice setting, nearly any increase in tumor size can be called progression and initiate change in therapy. Therefore, by the time progression is identified on the imaging, the tumor has been progressing for the previous 2-3 months without knowledge of treating physician. More frequent imaging raises the cost of clinical care and exposes patient to unnecessary radiation. Cell-free DNA in both plasma and serum has been found to be a good marker in lung cancer to evaluate response to therapy immediately after therapy is initiated, and therefore could be used to cause a more immediate change in therapy to improve outcomes. AC Electrokinetic (ACE) isolation and quantification of cell-free circulating DNA (CFC DNA) represents an attractive way to perform treatment response monitoring without increasing the cost. This project will focus on the aspect of using a proprietary ACE device to isolate and analyze CFC DNA from NSCLC patient blood. The specific aims for the Phase I proposal are: 1 - Determine day-to-day variability of ACE results. 2 - In a small human study, determine relationship between radiological estimate of change in tumor size and ACE estimate using blood sample data. A future Phase II proposal will construct an analytical system for commercialization, perform a 100 patient study where non-responders will be identified using the ACE technology and then switch the course of treatment to provide more favorable outcomes to the patient. The Phase II study will also develop a POC assay for FDA submission.