京都大学 · 医学
Shiro Takamatsu教授の研究室は、がんの個別化医療を推進するため、ホモロガス・レコンビネーション修復欠損(HRD)のバイオマーカーとしての臨床的意義を、がん全般にわたって包括的に解明しています。特に、卵巣がんや婦人科がんを対象としたHRDスコアやBRCA遺伝子変異の治療反応への影響を、TCCGやCCLEなどの大規模ゲノムデータベースを活用して解析しています。また、HRDと化学療法・PARP阻害剤感受性の関連性に疑問を呈する逆説的知見を提示し、治療意思決定の高度化に貢献しています。
Figures are computed from collected data and may differ slightly.
This study provides evidence for the usefulness of HRD analysis in all cancer types, improves chemotherapy decision making and its efficacy in clinical settings, and represents a substantial advancement in precision oncology.
Malignant psoas syndrome (MPS) is a rare and unique cancer-associated syndrome caused by the malignant involvement of the psoas major muscle, and is characterized by ipsilateral lumbosacral plexopathy and painful hip flexion. The pain in MPS is often distressing and intractable, and there is no established effective treatment approach. Herein, the present study reports on three cases of MPS associated with gynecological malignancies, wherein symptom improvement was observed following chemotherap
In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression in the serous subtype regardless of HRD status. The results suggest that in the first-line treatment, bevacizumab may be more beneficial in patients with a shorter prognosis who are less likely to experience the rebound outcome.
While large publicly available cancer cell line databases are invaluable for preclinical drug discovery and biomarker development, the association between homologous recombination deficiency (HRD) and drug sensitivity in these resources remains unclear. In this study, we comprehensively analyzed molecular profiles and drug screening data from the Cancer Cell Line Encyclopedia. Unexpectedly, gene alterations in BRCA1/2 or homologous recombination-related genes, HRD scores, or mutational signature
This study provides evidence for the usefulness of HRD analysis in all cancer types, improves chemotherapy decision making and its efficacy in clinical settings, and represents a substantial advancement in precision oncology.A comprehensive pan-cancer analysis on the clinical significance of homologous recombination deficiency.
Abstract Background Genomic alterations in BRCA1/2 and genomic scar signatures are associated with homologous recombination DNA repair deficiency (HRD) and serve as therapeutic biomarkers for platinum and PARP inhibitors in breast and ovarian cancers. However, the clinical significance of these biomarkers in other homologous recombination repair-related genes or other cancer types is not fully understood. Results We analyzed the datasets of all solid cancers from The Cancer Genome Atlas and Canc
Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome primarily caused by a tumor-producing parathyroid hormone-related protein (PTH-rP). We describe the first reported case of a uterine carcinosarcoma causing HHM. A 70-year-old patient was transferred to our hospital for a uterine tumor accompanied by impaired consciousness. The laboratory tests indicated anemia, malnutrition, elevated serum calcium and elevated PTH-rP. Emergency surgery, including abdominal hysterectomy and bi
The new tumor subtyping method can serve as a tumor-agnostic biomarker for ICI response prediction and will improve decision making in cancer treatment.
Approximately half of high-grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination deficiency (HRD) with characteristic genomic rearrangements. However, the impact of HRD on centromeres and transposable elements remains largely unexplored in HGSOC since conventional short-read sequencing is unable to interrogate these repetitive regions. We employed Oxford Nanopore long-read sequencing (LRS) to investigate genomic and epigenetic alterations in these regions. Pre-treatment a
Higher-resolution tumor-agnostic biomarkers that predict response to immune checkpoint inhibitor (ICI) therapy are needed. Mutation signatures reflect underlying oncogenic processes that can affect tumor immunogenicity, and thus potentially delineate ICI treatment response among tumor types. Systematic mutational signature analysis on all solid tumors in The Cancer Genome Atlas yielded eight distinct tumor genomic subtypes, which were characterized by smoking exposure, ultraviolet light exposure
Abstract Background Bevacizumab has been used in the first-line and recurrent treatment of ovarian cancer. However, the time-dependent changes in the effects of bevacizumab administration are not fully understood. Methods The ICON7-A cohort was generated from two ancillary analyses of the ICON7 trial. ICON7-A tumors were classified as homologous recombination deficient (HRD) or non-HRD based on their gene expression profiles. Kaplan-Meier curves from published phase III trials were graphically a
Abstract Background: Microsatellite instability (MSI) and tumor mutation burden (TMB) are being considered as predictive biomarkers for PD-1 and PD-L1 blockade immunotherapy. However, in ovarian clear-cell carcinoma (OCC), which demonstrates characteristic resistance to standard chemotherapy, the extent of MSI and TMB and their subsequent prognostic capability are unresolved. The aim of this study is to investigate TMB and MSI in OCC for improved therapy decision making. Methods: Tumor-normal pa
Abstract Although preclinical studies for drug discovery and biomarker development are extensively conducted using large publicly available cancer cell line databases, there have been no reports to date that clarify the association between homologous recombination repair deficiency (HRD) and drug sensitivity using these data. We comprehensively analyzed the molecular profiles and drug response screening data from the Cancer Cell Line Encyclopedia. Unexpectedly, gene alterations in BRCA1/2 or hom
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