ISY13-4 - Gene expression and mutation profiling for cancer of unknown primary

Abstract

Cancer of unknown primary site (CUP) is characterized as a metastatic cancer diagnosed without the primary site. As treatment for specific types of advanced cancer improves, it becomes increasingly that accurate identification of the tissue of origin and subsequent site-specific therapy may result in improved prognosis for patients with CUP. In addition, several tumor growth driving mutations have been identified for which inhibition of the target using molecular targeted drugs results in definite survival benefit for specific group of patients. We have now developed integrative algorithm using the next generation sequencer platform to identify gene expression-based cancer classifiers and detect known oncogenic driver mutations. We identified a molecular signature through genome-wide expression profiles and constructed a cancer classifier with weighted-voting system. Multicenter phase 2 clinical trial using this platform for CUP patients is now under investigation in 18 sites to determine the utility of treatment strategy using NGS. Additionally, targeting of the immune system has shown clinical benefit for several advanced solid tumors. Nevertheless, there is few research to establish the backgrounds of such treatment strategy using immuno-checkpoint inhibitors for CUP. We have now under investigation to evaluate immune-related factors for CUP. Our results suggested that prospective trial to evaluate the benefit of immuno-checkpoint inhibitor for CUP is warranted.