There is an increasing demand to understand cancer biology in clinic as genomic analysis and artificial intelligence have been incorporated into clinical practice. Physician-scientists are physicians who devote to identify new knowledge about health and disease and deliver new patient care through research by paying significant proportion of their professional efforts. Comprehensive genomic profiling (CGP) tests were approved by Japanese government two years ago. CGPs aim to provide patients with molecular targeting agents by analyzing 100-300 cancer related genes, however, the proportion of patient who enjoy benefit from the result of CGP test were about 10%. Therefore, the primary role of physician-scientist is to identify and develop new targeted therapies. In addition, physician-scientist can contribute to interpret the results of CGP tests properly by taking advantage of their knowledge in basic molecular biology. Thus, physician-scientist is expected to be a hub in precision medicine.

　In June 2019, the Japanese government reimbursed comprehensive genomic profiling（CGP）tests. While CGP tests have been incorporated into routine clinical.　The Challenges of Drug Provision in Cancer Genome Medicine practice, CGP tests are only available at designated hospitals. Moreover, the indication is restricted to patients with disease progression during standard therapies or without standard treatments. According to the data reported by the Ministry of Health, Labour and Welfare, the proportion of receiving genomically-matched therapies was 8.1% and the accessibility of matched therapies is a big issue in current precision oncology in Japan. To improve the drug accessibility, a prospective trial of patient-proposed healthcare services with multiple targeted agent（BELIEVE trial）is on-going at 12 designated core hospitals for genomic medicine.

　The comprehensive genomic profiling (CGP) test sometimes identifies pathogenic germline variants and presumed germline pathogenic variants, although its main purpose is to search for treatments based on somatic variants. Therefore, it is necessary for a cancer genome medical coordinator (CGMC) not only to explain the role of the CGP test to patients but also to mediate between cancer genomic and genetic medicine. However, there is a general shortage of educational establishments able to teach the required knowledge and skills. In this report, I discuss the importance and problems of mediating cancer genomic and genetic medicine. I also would like to introduce our training program to be the CGMC at Hyogo Cancer Center.

　Among liquid biopsies, circulating tumor DNA (ctDNA) analysis can identify genomic alterations with high accuracy. A ctDNA gene panel test has been approved in Japan and is expected to be used for cancer precision medicine in the future. In cancer genome profiling, ctDNA analysis has the advantages of faster turnaround time of results and evaluation of heterogeneity of genetic abnormalities compared to tumor tissue analysis. We have launched GOZILA, a ctDNA-based screening study, based on the GI-SCREEN platform, a national gastrointestinal cancer biomarker screening project of SCRUM-Japan. In a large-scale study comparing GOZILA and GI-SCREEN, we have shown that genomic profiling has the advantage of reducing the time to return results and increasing patient enrollment without compromising therapeutic efficacy. We have also experienced cases in which genomic abnormalities that could not be detected by tissue analysis were identified by ctDNA analysis, and therapeutic effects were observed by cancer genomic medicine based on these abnormalities. Based on the usefulness of ctDNA analysis, we are currently conducting a clinical trial of umbrella/basket type in patients with advanced solid tumors.

　There are few data on tumor development in relatives of Lynch syndrome (LS) probands in Japan. The aim of this retrospective study is to investigate the prevalence of LS-associated tumors in relatives of LS probands identified via universal tumor screening (UTS). Nineteen patients were diagnosed as having LS via UTS by immunohistochemical staining for DNA mismatch repair proteins of 2,141 tumors; including colorectal, endometrial, ovarian, upper urinary tract urothelial, and small-bowel cancers. We investigated the family tumor history of first-degree relatives (FDRs), second-degree relatives (SDRs), and third-degree relatives (TDRs) from 14 out of the 19 LS patients. There were 165 relatives (80 females); 58 FDRs，89 SDRs，and 18 TDRs. 39 relatives had 46 malignant tumors, of which 39 were LS-associated in 32 relatives. 31% (18/58) of FDRs, 11% (10/89) of SDRs, and 22% (4/18) TDRs had LS-associated tumors. Among FDRs and TDRs who had the tumors, tumor development was frequently seen in uterus (37% of females) colorectum (34%), and stomach (19%). FDRs in the older generation had significantly higher prevalence of LS-associated tumors compared with those in the younger or the same generation (FDRs：46 % vs 19%，P=0.04). The main sites of tumor development in relatives of LS were uterus, colorectum, and stomach in our study. In clinical practice for patients suggestive of LS, it seems important to take information about the medical history of their older generations.