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Characterization of Smoking-Associated Circulating Tumor DNA (ctDNA) for Lung Cancer

Institution: University of California, Los Angeles
Investigator(s): Jordan Cheng,
Award Cycle: 2019 (Cycle 30) Grant #: T30DT0908 Award: $151,350
Subject Area: Cancer
Award Type: Dissertation Awards

Initial Award Abstract
Lung cancer is a smoking-related disease and is currently the number one cause of mortality amongst all cancers. By the lung time cancer is usually detected, the patient presents with a late-stage diagnosis. Thus, screening in high-risk patients (such as smokers) to detect early stage lung cancer is sorely needed. Radiographic imaging can be used to screen for lung tumors, but they lack the ability to catch tumors early and do not provide any genetic information. Liquid biopsy, an emerging clinical concept, can solve this problem by non-invasively detecting lung cancer in bodily fluids by measuring circulating tumor DNA (ctDNA) fragments shed by tumor cells. We have developed a technology, electric field-induced release and measurement (EFIRM) liquid biopsy (eLB) which can reliably assess ctDNA of two major subtypes of lung cancer mutations using only a small volume of blood. These two major subtypes, however, only provide coverage for 15% of lung cancer subtypes. Therefore, effort must be made to expand the number detectable mutations and in particular, those associated with smoking such as KRAS mutations. The difficulty with expanding targets detectable by eLB is that it requires true clinical samples containing ctDNA from cancer patients. Various groups have attempted to fabricate artificial ctDNA with limited success. A major reason is because there is limited understanding of ctDNA biology in terms of its various traits. In this proposal we wish achieve four objectives. Firstly, we wish to complete development of an eLB assay for smoking-associated KRAS ctDNA and test its efficacy on clinical samples. Secondly, we wish to describe the biological characteristics of the smoking-associated KRAS ctDNA target in patient plasma samples that are detected by eLB. Thirdly, we wish to observe the similarity between the biology in ctDNA from clinical samples and cultured cell harboring the same smoking-associated KRAS. Finally, we wish to attempt to use this cell culture to create a surrogate KRAS ctDNA model that can be used as standardized material for ctDNA detection development. The findings from this project will be essential for learning more about ctDNA and cancer biology and will aid in expanding EFIRM's panel of ctDNA targets. This will help advance a clinical liquid biopsy approach for early detection for smoking-associated lung cancer.