著者

Atsushi OHTSU Koichi GOTO Takayuki YOSHINO

出版者

The Japan Academy

雑誌

Proceedings of the Japan Academy, Series B (ISSN:03862208)

巻号頁・発行日

pp.pjab.99.015, (Released:2023-08-09)

被引用文献数

2

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Cancer comprehensive genomic profiling (CGP) is a fundamental tool for promoting precision oncology in advanced solid tumors. In 2015, we launched the SCRUM-Japan platform for CGP test screening followed by enrollment in genomically-matched clinical trials. More than 30,000 tissue-based and 10,000 liquid-based CGP tests have already been performed for enrollment in a total of 127 industry-/investigator-initiated registration trials. So far, 12 new agents with 14 indications have achieved regulatory approval for health care coverage in Japan. Using the clinical-genomic database of this project, a new driver gene was recently discovered with a dramatic response to a genomically-matched agent. Liquid biopsies are a potentially powerful tool for establishing precision oncology. Our comparative study with tissue-based CGPs revealed the utility of liquid biopsy in terms of being less invasive, shorter turn-round time, and higher enrollment rate for genotype-matched treatment than tissue-based CGP in gastrointestinal cancers. Another major multilayer multi-omics study (MONSTAR-SCREEN-2) including whole exome/transcriptome tissue- and liquid-based analyses and multiplex immunohistochemistry, with artificial intelligence/machine learning was launched in 2020 for the purpose of novel biomarker and new oncology agent discovery/development in collaboration with 18 pharmaceutical companies.For detecting minimal/molecular residual disease (MRD) after surgery, post-surgical monitoring with tumor-informed liquid biopsy assays in association with two randomized controlled trials also started in 2020 (CIRCULATE-Japan). More than 5,000 patients have already been enrolled and the observational cohort study showed the clear utility of MRD monitoring for predicting recurrence, leading to changes in clinical practice in patient selection regarding who should receive adjuvant therapy in the near future.

著者

Keiko MAEKAWA Masaya ITODA Kimie SAI Yoshiro SAITO Nahoko KANIWA Kuniaki SHIRAO Tetsuya HAMAGUCHI Hideo KUNITOH Noboru YAMAMOTO Tomohide TAMURA Hironobu MINAMI Kaoru KUBOTA Atsushi OHTSU Teruhiko YOSHIDA Nagahiro SAIJO Naoyuki KAMATANI Shogo OZAWA Jun-ichi SAWADA

出版者

The Japanese Society for the Study of Xenobiotics

雑誌

Drug Metabolism and Pharmacokinetics (ISSN:13474367)

巻号頁・発行日

vol.21, no.2, pp.109-121, 2006 (Released:2006-05-10)

参考文献数

35

被引用文献数

36

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The ATP-binding cassette transporter, ABCG2, which is expressed at high levels in the intestine and liver, functions as an efflux transporter for many drugs, including clinically used anticancer agents such as topotecan and the active metabolite of irinotecan (SN-38). In this study, to elucidate the linkage disequilibrium (LD) profiles and haplotype structures of ABCG2, we have comprehensively searched for genetic variations in the putative promoter region, all the exons, and their flanking introns of ABCG2 from 177 Japanese cancer patients treated with irinotecan. Forty-three genetic variations, including 11 novel ones, were found: 5 in the 5′-flanking region, 13 in the coding exons, and 25 in the introns. In addition to 9 previously reported nonsynonymous single nucleotide polymorphisms (SNPs), 2 novel nonsynonymous SNPs, 38C>T (Ser13Leu) and 1060G>A (Gly354Arg), were found with minor allele frequencies of 0.3%. Based on the LD profiles between the SNPs and the estimated past recombination events, the region analyzed was divided into three blocks (Block -1, 1, and 2), each of which spans at least 0.2 kb, 46 kb, and 13 kb and contains 2, 24, and 17 variations, respectively. The two, eight, and five common haplotypes detected in 10 or more patients accounted for most (>90%) of the haplotypes inferred in Block -1, Block 1, and Block 2, respectively. The SNP and haplotype distributions in Japanese were different from those reported previously in Caucasians. This study provides fundamental information for the pharmacogenetic studies investigating the relationship between the genetic variations in ABCG2 and pharmacokinetic/pharmacodynamic parameters.