Article
Oncology
Shujing Li, Sien Zhao, Nianhai Liang, Shaoting Zhang, Liangying Zhang, Liangji Zhou, Anbu Liu, Xu Cao, Jinhai Tian, Yuanyuan Yu, Zhaoyang Fan, Kun Xiao, Ming Wang, Hui Zhao, Ru Bai, Jianmin Sun
Summary: In this study, the researchers investigated the role of SPRY4 in GISTs and its related mechanisms. They found that SPRY4 inhibits the expression and activation of KIT in GISTs, leading to decreased cell survival and proliferation. Additionally, SPRY4 enhances the inhibitory effect of Imatinib on primary KIT mutants, but has no effect on drug-resistant secondary KIT mutants.
Article
Biochemistry & Molecular Biology
Anbu Liu, Shaoting Zhang, Ming Wang, Liangying Zhang, Shidong Xu, Ahmad Nasimian, Shujing Li, Sien Zhao, Xu Cao, Jinhai Tian, Yuanyuan Yu, Zhaoyang Fan, Kun Xiao, Hui Zhao, Julhash U. Kazi, Lijun Ma, Jianmin Sun
Summary: This study demonstrates that DDR1/2 contribute to KIT activation and enhance resistance to imatinib in GISTs, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.
MOLECULAR CARCINOGENESIS
(2023)
Article
Oncology
Juan Liu, Jingjing Gao, Aoli Wang, Zongru Jiang, Shuang Qi, Ziping Qi, Feiyang Liu, Kailin Yu, Jiangyan Cao, Cheng Chen, Chen Hu, Hong Wu, Li Wang, Wenchao Wang, Qingsong Liu, Jing Liu
Summary: Drug resistance is a major challenge in the treatment of gastrointestinal stromal tumours (GISTs). A study has found that nintedanib can overcome resistance caused by mutations in the KIT gene and upregulation of fibroblast growth factor (FGF) activity. Nintedanib also showed inhibitory effects on cell proliferation and ERK phosphorylation in preclinical GIST models.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Lorena Incorvaia, Dario De Biase, Margherita Nannini, Elena Fumagalli, Bruno Vincenzi, Ida De Luca, Chiara Brando, Alessandro Perez, Maria A. Pantaleo, Silvia Gasperoni, Lorenzo D'Ambrosio, Giovanni Grignani, Thais Maloberti, Erika Pedone, Tancredi Didier Bazan Russo, Alessandro Mazzocca, Laura Algeri, Alessandra Dimino, Nadia Barraco, Roberta Serino, Valerio Gristina, Antonio Galvano, Viviana Bazan, Antonio Russo, Giuseppe Badalamenti
Summary: This study investigated the prognostic role of KIT or PDGFRA-VAF in GIST patients and found that higher VAF levels were independent predictors of poor prognosis and survival in localized GIST patients with KIT or PDGFRA mutations. This study is important for the prognostication and choice of adjuvant treatment in patients with gastrointestinal stromal tumors.
Article
Biochemistry & Molecular Biology
Wangzhen He, Liangliang Xu, Jiongyan Ding, Li Song, Weili Yang, Isabella Klooster, Daniel F. Pilco-Janeta, Cesar Serrano, Hongming Fang, Guojun Jiang, Xiaoyan Wang, Jiren Yu, Wen-Bin Ou
Summary: Most GISTs have mutations in the receptor tyrosine kinase KIT/PDGFRA, which provides a potential target for therapy. However, these tumors often develop resistance to the KIT/PDGFRA inhibitor imatinib. This study found that the non-RTK activated kinase ACK1 is overexpressed in GISTs. Inhibition of ACK1 using a specific inhibitor or siRNA suppressed cell viability and migration, and also inhibited signaling pathways and epithelial-mesenchymal transition. Co-targeting ACK1 and KIT showed additive effects in suppressing proliferation and promoting apoptosis, as well as inhibiting invasiveness and migration in GIST cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Oncology
Inga-Marie Schaefer, Matthew L. Hemming, Meijun Z. Lundberg, Matthew P. Serrata, Isabel Goldaracena, Ninning Liu, Peng Yin, Joao A. Paulo, Steven P. Gygi, Suzanne George, Jeffrey A. Morgan, Monica M. Bertagnolli, Ewa T. Sicinska, Chen Chu, Shanshan Zheng, Adrian Marino-Enriquez, Jason L. Hornick, Chandrajit P. Raut, Wen-Bin Ou, George D. Demetri, Sinem K. Saka, Jonathan A. Fletcher
Summary: The study identifies recurrent genomic aberrations in cell cycle regulators causing co-activation of the CDK2 and CDK4/6 pathways in clinical GIST samples. Therapeutic co-targeting of CDK2 and CDK4/6 is synergistic in GIST cell lines with intact RB1, through inhibition of RB1 hyperphosphorylation and cell proliferation. RB1 inactivation and a novel oncogenic cyclin D1 resulting from an intragenic rearrangement (CCND1::chr11.g:70025223) are mechanisms of acquired CDK-inhibitor resistance in GIST.
BRITISH JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Chi Yan, Chengzhi Zhao, Ke Yang, Hongyan Zhou, Limin Jing, Weixing Zhao, Wenguang Dou, Qingxin Xia, Jie Ma, Bing Wei, Yongjun Guo
Summary: This study identified two rare c-KIT gene mutations in GIST and melanoma patients, which play a novel role in resistance to imatinib, expanding the clinical research field.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Oncology
Bayan Al-Share, Abdulrahman Alloghbi, Mohammed Najeeb Al Hallak, Hafiz Uddin, Asfar Azmi, Ramzi M. Mohammad, Steve H. Kim, Anthony F. Shields, Philip A. Philip
Summary: GIST is a rare tumor originating from the interstitial cells of Cajal in the gastrointestinal tract, with surgery being the only curative treatment for localized disease. Targeted therapies like imatinib have shown improved survival rates in patients. FDA-approved new tyrosine kinase inhibitors, avapritinib and ripretinib, provide options for heavily pretreated advanced GIST. Future shifts in therapy paradigms are likely to occur in the treatment of GIST.
CANCER AND METASTASIS REVIEWS
(2021)
Article
Oncology
Sebastian Bauer, Michael C. Heinrich, Suzanne George, John R. Zalcberg, Cesar Serrano, Hans Gelderblom, Robin L. Jones, Steven Attia, Gina D'Amato, Ping Chi, Peter Reichardt, Julie Meade, Ying Su, Rodrigo Ruiz-Soto, Jean-Yves Blay, Margaret von Mehren, Patrick Schoffski
Summary: This study reports the genomic heterogeneity of tumors from patients with advanced GIST and evaluates the efficacy of ripretinib across different KIT/PDGFRA mutation subgroups. Ripretinib demonstrated progression-free survival benefit in all assessed subgroups, including those with wild-type KIT/PDGFRA by tumor tissue.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Susanne Grunewald, Lillian R. Klug, Thomas Muhlenberg, Jonas Lategahn, Johanna Falkenhorst, Ajia Town, Christiane Ehrt, Eva Wardelmann, Wolfgang Hartmann, Hans-Ulrich Schildhaus, Juergen Treckmann, Jonathan A. Fletcher, Sascha Jung, Paul Czodrowski, Stephen Miller, Oleg Schmidt-Kittler, Daniel Rauh, Michael C. Heinrich, Sebastian Bauer
Summary: Avapritinib shows substantial clinical activity in patients with PDGFRA D842V genotype, but secondary resistance has been observed. Some PDGFRA mutant patients develop secondary mutations that interfere with avapritinib binding, leading to resistance.
Article
Multidisciplinary Sciences
Atish Mohanty, Arin Nam, Saumya Srivastava, Jeff Jones, Brett Lomenick, Sharad S. Singhal, Linlin Guo, Hyejin Cho, Aimin Li, Amita Behal, Tamara Mirzapoiazova, Erminia Massarelli, Marianna Koczywas, Leonidas D. Arvanitis, Tonya Walser, Victoria Villaflor, Stanley Hamilton, Isa Mambetsariev, Martin Sattler, Mohd W. Nasser, Maneesh Jain, Surinder K. Batra, Raffaella Soldi, Sunil Sharma, Marwan Fakih, Saswat Kumar Mohanty, Avijit Mainan, Xiwei Wu, Yihong Chen, Yanan He, Tsui-Fen Chou, Susmita Roy, John Orban, Prakash Kulkarni, Ravi Salgia
Summary: This study reveals non-genetic mechanisms of resistance to sotorasib and proposes a treatment strategy to enhance sensitivity by targeting both ITGB4 and beta-catenin.
Article
Oncology
Jiawan Wang, Kai Pollard, Ana Calizo, Christine A. Pratilas
Summary: The study demonstrates that the combination of MEK and MET inhibitors may delay or prevent acquired resistance to MEK inhibitors through a novel mechanism, with clinical implications for MPNST patients with NF1 alterations.
Article
Oncology
Vaibhav Kumar, Leslie Doros, Margaret Thompson, Sirisha L. Mushti, Rosane Charlab, Elizabeth I. Spehalski, Hong Zhao, Matthew D. Thompson, Shenghui Tang, Richard Pazdur, Steven J. Lemery, Marc R. Theoret, Lola A. Fashoyin-Aje
Summary: On May 15, 2020, the FDA approved ripretinib for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with three or more kinase inhibitors, including imatinib. The approval was based on results from the INVICTUS trial, which showed a significant improvement in progression-free survival for patients in the ripretinib group compared to the placebo group. The median overall survival was also longer in the ripretinib group.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Mariarita Sciume, Giusy Ceparano, Cristina Eller-Vainicher, Sonia Fabris, Silvia Lonati, Giorgio Alberto Croci, Luca Baldini, Federica Irene Grifoni
Summary: Systemic mastocytosis (SM) is a rare neoplasm with heterogeneous clinical features, requiring individualized treatment. A patient with indolent SM developed a myeloid neoplasm with PDGFRA rearrangement, achieving complete remission with low-dose imatinib treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Sercan Ergun, Oguzhan Akgun, Neslihan Taskurt Hekim, Senanur Aslan, Ferda Ari, Sezgin Gunes, Ummet Abur
Summary: In this study, it was found that miR-128/193a-5p/494 may be associated with imatinib resistance in prostate cancer. Specifically, the upregulation of FYN may suppress the transcriptional activity of miR-128/193a-5p/494. Thus, miR-128/193a-5p/494 may play a critical role in imatinib resistance through the tr-KIT pathway.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Akira Sawaki, Toshirou Nishida, Toshihiko Doi, Yasuhide Yamada, Yoshito Komatsu, Tatsuo Kanda, Yoshihiro Kakeji, Yusuke Onozawa, Makoto Yamasaki, Atsushi Ohtsu
Article
Oncology
Ken Kato, Kei Muro, Keiko Minashi, Atsushi Ohtsu, Satoshi Ishikura, Narikazu Boku, Hiroya Takiuchi, Yoshito Komatsu, Yoshinori Miyata, Haruhiko Fukuda
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2011)
Article
Oncology
Kohei Shitara, Satoshi Yuki, Motoki Yoshida, Daisuke Takahari, Setsuo Utsunomiya, Tomoya Yokota, Yozo Sato, Yoshitaka Inaba, Masahiro Tajika, Hiroki Kawai, Hidekazu Yamaura, Mina Kato, Kentaro Yamazaki, Yoshito Komatsu, Kei Muro
INVESTIGATIONAL NEW DRUGS
(2012)
Article
Oncology
Kohei Shitara, Isao Oze, Ayako Mizota, Chihiro Kondo, Motoo Nomura, Tomoya Yokota, Daisuke Takahari, Takashi Ura, Satoshi Yuki, Yoshito Komatsu, Keitaro Matsuo, Kei Muro
JAPANESE JOURNAL OF CLINICAL ONCOLOGY
(2011)
Article
Oncology
Susumu Sogabe, Yoshito Komatsu, Satoshi Yuki, Takaya Kusumi, Kazuteru Hatanaka, Michio Nakamura, Takashi Kato, Takuto Miyagishima, Ayumu Hosokawa, Ichiro Iwanaga, Yuh Sakata, Masahiro Asaka
JAPANESE JOURNAL OF CLINICAL ONCOLOGY
(2011)
Article
Oncology
Yoshito Komatsu, Satoshi Yuki, Susumu Sogabe, Hiraku Fukushima, Ichiro Iwanaga, Mineo Kudo, Miki Tateyama, Takashi Meguro, Minoru Uebayashi, Akiyoshi Saga, Yuh Sakata, Masahiro Asaka
Article
Oncology
Akihito Kawazoe, Yasutoshi Kuboki, Eiji Shinozaki, Hiroki Hara, Tomohiro Nishina, Yoshito Komatsu, Satoshi Yuki, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Takeshi Kuwata, Masahito Kawazu, Hiroyuki Mano, Yosuke Togashi, Hiroyoshi Nishikawa, Takayuki Yoshino
CLINICAL CANCER RESEARCH
(2020)
Article
Medicine, General & Internal
Shintaro Nakano, Yoshito Komatsu, Yasuyuki Kawamoto, Rika Saito, Ken Ito, Hiroshi Nakatsumi, Satoshi Yuki, Naoya Sakamoto
Article
Oncology
Hisato Kawakami, Shuichi Hironaka, Taito Esaki, Kazuaki Chayama, Masahiro Tsuda, Naotoshi Sugimoto, Shigenori Kadowaki, Akitaka Makiyama, Nozomu Machida, Hidekazu Hirano, Kenro Hirata, Hiroki Hara, Hiroshi Yabusaki, Yoshito Komatsu, Kei Muro
Summary: The study focuses on investigating the efficacy and safety of nivolumab plus low-dose ipilimumab for MSI-H GC in the first-line setting, with the primary objective being to determine the overall response rate.
Article
Medicine, Research & Experimental
Yoshito Komatsu, Shuichi Hironaka, Yoshinori Tanizawa, Zhihong Cai, Yongzhe Piao, Narikazu Boku
Summary: In real-world treatment practice for advanced gastric cancer in Japan, therapy choices were consistent with guidelines for the first-line chemotherapy. Factors associated with overall therapy duration were identified, providing valuable insights for optimizing treatment sequence.
ADVANCES IN THERAPY
(2022)
Article
Oncology
Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Yosuke Togashi, Shohei Koyama, Daisuke Kotani, Shota Fukuoka, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Makoto Fukui, Masashi Wakabayashi, Naoki Nakamura, Motohiro Kojima, Hiroshi Kawachi, Richard Kirsch, Tsutomu Yoshida, Yutaka Suzuki, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Summary: The study suggests that consolidation treatment with nivolumab after CRT can increase the pCR rate in patients with rectal cancer. PD-L1 expression and an elevated CD8/eTreg ratio are positive predictors in patients with MSS rectal cancer.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yoshiaki Nakamura, Wataru Okamoto, Takeshi Kato, Taito Esaki, Ken Kato, Yoshito Komatsu, Satoshi Yuki, Toshiki Masuishi, Tomohiro Nishina, Hiromichi Ebi, Kentaro Sawada, Hiroya Taniguchi, Nozomu Fuse, Shogo Nomura, Makoto Fukui, Seiko Matsuda, Yasutoshi Sakamoto, Hiroshi Uchigata, Kana Kitajima, Naomi Kuramoto, Takashi Asakawa, Steve Olsen, Justin Odegaard, Akihiro Sato, Satoshi Fujii, Atsushi Ohtsu, Takayuki Yoshino
Summary: The study demonstrated that ctDNA genotyping can identify mCRC patients who benefit from pertuzumab plus trastuzumab treatment and monitor treatment response. The accuracy of ctDNA genotyping in identifying HER2-amplified mCRC patients was similar to tissue genotyping.
Article
Gastroenterology & Hepatology
Kensuke Sakurai, Takehiko Katsurada, Mutsumi Nishida, Satomi Omotehara, Shinya Fukushima, Shinsuke Otagiri, Kazunori Nagashima, Reizo Onishi, Ryo Takagi, Yoshito Komatsu, Naoya Sakamoto
Summary: This study aimed to determine the features of ultrasound findings in immune-mediated colitis (IMC) and examine their correlation with colonoscopy findings and severity of colitis. The results showed significant correlations between ultrasound findings, colonoscopy findings, and severity of colitis.
INTESTINAL RESEARCH
(2022)
Article
Oncology
Kohei Shitara, Motohiro Hirao, Satoru Iwasa, Takashi Oshima, Yoshito Komatsu, Akihito Kawazoe, Yasuyoshi Sato, Takuya Hamakawa, Kan Yonemori, Nozomu Machida, Satoshi Yuki, Takuya Suzuki, Shiori Okumura, Takao Takase, Taro Semba, Bob Zimmermann, Angela Teng, Kensei Yamaguchi
Summary: In this phase I study, the efficacy and safety of E7389-LF in Japanese patients with advanced gastric cancer were explored. The results showed that E7389-LF demonstrated preliminary activity in the treatment of gastric cancer patients, but further research is needed.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Kanako Hagio, Junko Kikuchi, Kohichi Takada, Hiroki Tanabe, Minako Sugiyama, Yoshihito Ohhara, Toraji Amano, Satoshi Yuki, Yoshito Komatsu, Takahiro Osawa, Kanako C. Hatanaka, Yutaka Hatanaka, Takashi Mitamura, Ichiro Yabe, Yoshihiro Matsuno, Atsushi Manabe, Akihiro Sakurai, Atsushi Ishiguro, Masato Takahashi, Hiroshi Yokouchi, Hirohito Naruse, Yusuke Mizukami, Hirotoshi Dosaka-Akita, Ichiro Kinoshita
Summary: Comprehensive genomic profiling (CGP) tests are covered by public insurance in Japan for patients with advanced solid tumors. However, genotype-matched drug candidates are often unapproved or off-label, making clinical trial access critical. To address this, previous treatment data was analyzed, revealing that the timing of CGP tests affects clinical trial eligibility, especially for breast and prostate cancers.