Cancer treatment is rapidly proceeding towards the era of personalized medicine where treatment is based on the distinctive molecular characteristics of a patient's tumor. The data from this project will be used to construct networks that will include gene expression profiles of lung tumors. These networks will capture the complexity of somatic events intrinsic to the tumor layered over the genetic background that is inherent to the individual. This knowledge will help to more accurately predict disease outcome so that patients at high risk of relapse will receive the most aggressive treatment. It will also allow patients to receive novel combinations of therapies that will afford maximum treatment.
Building on the work of "Lung Cancer System Genetics Project" that was funded by The Bonnie J. Addario Lung Cancer Foundation, the Kim Lab employs sophisticated system genetics/genomics approaches in lung and other human cancers to develop predictive and prognostic molecular markers for diagnostic and therapeutic application.The Kim lab studies genome-wide gene expression, DNA copy number, mutation, fusions, and any other genetic changes in lung cancer. The lab has identified several novel molecular targets in normal and matched adenocarcinoma tissue, and is now working on functional and biological validation of these markers. This research is being used to develop novel therapeutic drugs and diagnostic assays for lung adenocarcinoma.
Next Generation Sequencing (NGS)
NGS holds great promise for cancer prevention. For example, screening readily available blood samples for mutation analysis or methylation activity has great potential in early detection. Although the presence of CTC (circulating tumor cell) has shown promise in malignancies such as breast cancer, there is, as yet, no clinically-approved blood test using mutation or methylation analysis to detect cancers at a curable early stage. In lung cancer, for example, a screening assay for either EGFR and K-ras, mutually exclusive makers, could, in theory, detect approximately one-half of all lung adenocarcinomas.
Such exquisitely sensitive genetic/genomic methods using "deep sequencing" (i.e. 500X coverage sequencing in blood or sputum) have the potential to dramatically improve methods of early detection and the more rapid identification of biomarkers. This is especially true in lung cancer where Dr. Kim envisions the use of NGS to detect early lung cancer. The UCSF Thoracic Oncology Program recently took a giant step forward in this regard with the acquisition of two state-of-the-art NGS machines, SOLID 5500 and Ion Torrent, a development that be of inestimable value in supporting Dr. Kim's research goals.
One-Shot Mutation Plate (OSMP) Development in Lung Cancer
While Dr. Kim was able to accomplish much in Korea in the development of genetic assays, that country lacked the pharmaceutical and biotech infrastructure to make these tests widely available. Dr. Kim therefore made the decision to move his research to the U.S. Ultimately, Dr. David Jablons at UCSF recruited Dr. Kim to join the faculty there as an Assistant Adjunct Professor of Surgery and to build a program in applied genomics. At UCSF, among other accomplishments, Dr. Kim developed a mutation plate for five frequently mutated genes in lung cancer including EGFR, associated with a clinical response to the drug Tarceva, and K-ras, associated with response to chemotherapy. Dr. Kim believes that OSMP may also be useful in early detection.