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Tetsuji Terazawa Takeshi Kato Masahiro Goto Katsuya Ohta Shingo Noura Hironaga Satake Yoshinori Kagawa Hisato Kawakami Hiroko Hasegawa Kazuhiro Yanagihara Tatsushi Shingai Ken Nakata Masahito Kotaka Masayuki Hiraki Ken Konishi Shiro Nakae Daisuke Sakai Yukinori Kurokawa Toshio Shimokawa Taroh Satoh 《The oncologist》2021,26(1):17-e47
Lessons Learned
- Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
- It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.
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Takeshi Nagashima Ken Yamaguchi Kenichi Urakami Yuji Shimoda Sumiko Ohnami Keiichi Ohshima Tomoe Tanabe Akane Naruoka Fukumi Kamada Masakuni Serizawa Keiichi Hatakeyama Kenya Matsumura Shumpei Ohnami Koji Maruyama Tohru Mochizuki Masatoshi Kusuhara Akio Shiomi Yasuhisa Ohde Masanori Terashima Katsuhiko Uesaka Tetsuro Onitsuka Seiichiro Nishimura Yasuyuki Hirashima Nakamasa Hayashi Yoshio Kiyohara Yasuhiro Tsubosa Hirohisa Katagiri Masashi Niwakawa Kaoru Takahashi Hiroya Kashiwagi Masahiro Nakagawa Yuji Ishida Takashi Sugino Mitsuru Takahashi Yasuto Akiyama 《Cancer science》2020,111(2):687-699
This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients. 相似文献
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Hsin-Yi Tseng Jan Dreyer Abdullah Al Emran Dilini Gunatilake Mehdi Pirozyan Carleen Cullinane Ken Dutton-Regester Helen Rizos Nicholas K. Hayward Grant McArthur Peter Hersey Jessamy Tiffen Stuart Gallagher 《International journal of cancer. Journal international du cancer》2020,147(8):2176-2189
The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti-apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra-terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti-apoptotic targets regulated by NF-kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro-apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I-BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3-only protein, BIM, and downregulated anti-apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT-199 or ABT-263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I-BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance. 相似文献
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Tada Kazuhiro Iwashita Yukio Shiraiwa Ken Uchida Hiroki Oshima Yusuke Sato Yuhki Nakanuma Hiroaki Hirashita Teijiro Masuda Takashi Endo Yuichi Takeuchi Yu Ohta Masayuki Itoh Hiroki Inomata Masafumi 《Cancer chemotherapy and pharmacology》2020,85(2):345-352
Cancer Chemotherapy and Pharmacology - Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired... 相似文献
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Tatsuaki Takeda Hiromasa Yamamoto Ken Suzawa Shuta Tomida Shunsaku Miyauchi Kota Araki Kentaro Nakata Akihiro Miura Kei Namba Kazuhiko Shien Junichi Soh Tadahiko Shien Yoshihisa Kitamura Toshiaki Sendo Shinichi Toyooka 《Cancer science》2020,111(3):849-856
Molecular‐targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan‐HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2‐positive breast cancer. However, acquired resistance of various cancers to molecular‐targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib‐resistant cell lines from HER2‐amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib‐resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1‐amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2‐targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome. 相似文献
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目的建立UPLC-PDA法同时测定复方五凤草液(五凤草、白芨、猫爪草)中没食子酸、原儿茶酸、对羟基苯甲酸、咖啡酸、金丝桃苷、槲皮素、柚皮素的含有量。方法该药物80%甲醇提取液的分析采用Waters BEH C18色谱柱(2.1 mm×100 mm, 1.7μm);流动相乙腈-0.1%甲酸,梯度洗脱;体积流量0.3 mL/min;柱温40℃;检测波长266 nm。结果 7种成分在各自范围内线性关系良好(r≥0.999 5),平均加样回收率96.96%~102.26%,RSD 0.65%~2.10%。结论该方法稳定准确,重复性好,可用于复方五凤草液的质量控制。 相似文献
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