Progress in genomic analysis are expected to improve the treatment outcome of cancers of unknown primary(CUP). We conducted a randomized phase Ⅱ trial of carboplatin plus paclitaxel versus site-specific therapy based on gene expression profiling(GEP)in patients with CUP. A phase Ⅱ trial was conducted in patients with CUP to evaluate the feasibility of site- specific therapy based on NGS-based primary site prediction from GEPs, including irGEP. We proposed the possibility of treatment with immune checkpoint inhibitors for CUP patients. Based on the results, a physician-led clinical trial of nivolumab for CUP was conducted with favorable results.

Neurofibromatosis type 2(NF2)is a hereditary condition that causes bilateral vestibular schwannomas(VS), multiple schwannomas, and meningiomas. The prognosis is poor because the multiplicity of the tumors leads to a progressive decline in the quality of life, deafness, and death in an early age. NF2 is caused by a disorder in the tumor suppressor gene NF2, which encodes the merlin protein. Although it is an autosomal dominant disease, more than half of cases are presumed to be de novo caused by somatic mosaicism, the diagnosis rate of which has been improved by the recently introduced technology of targeted deep sequencing of DNA from multiple tissues. No chemotherapeutic drugs for treating NF2-related VS are available at present, and surgery and radiotherapy remain the only therapeutic options. Recently, a randomized, double-blind, multicenter clinical trial has started in Japan to verify the efficacy and safety of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, in treating NF2-related VS.

There has been remarkable progress in systemic therapy for advanced lung cancer in recent years. Novel molecular targeted agents directed against oncogenic driver mutations as well as combination strategies with immune checkpoint inhibitors have been continuously emerged in the clinical practice, which is driving the expansion of precision medicine. As most of these newly developed drugs and therapies were approved on the basis of global randomized studies, the robust data for the efficacy and safety focused on the Japanese patients are limited. Given that the genetic, environmental, and social backgrounds of the Japanese are different from those of Caucasians, it is questionable whether the available global data for the efficacy and safety of newly developed drugs can passively be extrapolated to the Japanese patients. In this article, we discuss the regional and racial differences of the responses or toxicity profiles of anti-cancer agents, and review the characteristics of the Japanese subgroup data in global clinical studies focusing on the following 3 different types of drugs: epidermal growth factor receptor-tyrosine kinase inhibitors, cytotoxic chemotherapeutic agents, and immune checkpoint inhibitors.