Article
Multidisciplinary Sciences
Chinock Cheong, Jeonghyun Kang, Byung Soh Min, Nam Kyu Kim, Joong Bae Ahn, Kang Young Lee
Summary: This study investigated the impact of neoadjuvant imatinib on rectal GIST. The results showed that imatinib treatment can reduce tumor size, increase resectability, and help preserve the sphincter. The neoadjuvant group had a higher rate of levator ani muscle displacement and larger radiologic tumor size compared to the control group. However, there was no significant difference between the two groups in terms of postoperative complications, hospital stay, local recurrence, and disease-free survival.
Article
Oncology
Marya Kozinova, Shalina Joshi, Shuai Ye, Martin G. Belinsky, Dinara Sharipova, Jeffrey M. Farma, Sanjay S. Reddy, Samuel Litwin, Karthik Devarajan, Alex Rosa Campos, Yi Yu, Brian Schwartz, Margaret von Mehren, Lori Rink
Summary: This study evaluated the combination of a novel AKT inhibitor, MK-4440, with imatinib mesylate (IM) in gastrointestinal stromal tumor (GIST) cells and preclinical models. The results demonstrated synergistic effects of dual inhibition of KIT and AKT in both IM-sensitive and -resistant GIST cell lines, with enhanced cell death through cell cycle arrest and increased PDCD4 expression. In vivo studies showed superior efficacy of the MK-4440/IM combination in IM-sensitive GIST models, suggesting potential clinical benefits in primary GIST treatment.
Article
Oncology
Seong-Ho Kong, Yukinori Kurokawa, Jeong-Hwan Yook, Haruhiko Cho, Oh-Kyoung Kwon, Toru Masuzawa, Kyung Hee Lee, Sohei Matsumoto, Young Soo Park, Hiroshi Honda, Seung-Wan Ryu, Takashi Ishikawa, Hye Jin Kang, Kazuhito Nabeshima, Seock-Ah Im, Toshio Shimokawa, Yoon-Koo Kang, Seiichi Hirota, Han-Kwang Yang, Toshirou Nishida
Summary: This study confirms that neoadjuvant imatinib treatment is an effective option for gastric GISTs. It reduces tumor size and increases the rate of R0 resection. Postoperative imatinib treatment is recommended to minimize the risk of recurrence.
Review
Cell Biology
Jiehan Li, Shuning Guo, Zhenqiang Sun, Yang Fu
Summary: In this review, the role of noncoding RNAs (ncRNAs) in drug resistance of gastrointestinal stromal tumor (GIST) was summarized. The study found that ncRNAs play important roles in the resistance of GIST, mainly through regulating mechanisms such as oxidative phosphorylation, autophagy, apoptosis, drug target changes, and signaling pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Jean-Yves Blay, Yoon-Koo Kang, Toshiroo Nishida, Margaret von Mehren
Summary: Gastrointestinal stromal tumours (GIST) are rare malignancies with 80% of cases having KIT or PDGFRA activating mutations. Localized GIST can be cured through surgery, while advanced resistant GIST with resistance mutations require treatment with new drugs.
NATURE REVIEWS DISEASE PRIMERS
(2021)
Article
Medicine, Research & Experimental
Yu Zhao, Zuyi Weng, Xuan Zhou, Zhi Xu, Bei Cao, Bin Wang, Juan Li
Summary: Gastrointestinal stromal tumors (GISTs) are common sarcomas of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) therapy has been established as the adjuvant therapy for GISTs, but post-treatment resistance is a challenge. This study reveals the association between MSC in the tumor microenvironment and GIST drug resistance, and uncovers the underlying mechanism.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Yu Fu, Marie Karanian, Raul Perret, Axel Camara, Francois Le Loarer, Myriam Jean-Denis, Isabelle Hostein, Audrey Michot, Francoise Ducimetiere, Antoine Giraud, Jean-Baptiste Courreges, Kevin Courtet, Yech'an Laizet, Etienne Bendjebbar, Jean Ogier Du Terrail, Benoit Schmauch, Charles Maussion, Jean-Yves Blay, Antoine Italiano, Jean-Michel Coindre
Summary: Risk assessment of GIST relies on laborious mitotic counts and costly molecular testing, but both methods have limitations. Therefore, new methods, such as deep learning models trained on digitized whole slide images, are crucial for improving therapy tailoring and precision medicine for GIST patients. The DL models showed promising results in predicting patients' outcome, stratifying risk groups, and predicting specific mutations.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Gustav Johansson, Marta Berndsen, Stefan Lindskog, Tobias Osterlund, Henrik Fagman, Andreas Muth, Anders Stahlberg
Summary: A sequencing strategy based on molecular barcodes and a GIST-specific panel were utilized to monitor tumor-specific and TKI resistance mutations in patients with GISTs. High-risk patients were more likely to have detectable ctDNA, which became negative after surgery. This approach could be clinically useful in monitoring treatment efficacy and guiding treatment decisions.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Matthew L. Hemming, Shannon Coy, Jia-Ren Lin, Jessica L. Andersen, Joanna Przybyl, Emanuele Mazzola, Amr H. Abdelhamid Ahmed, Matt van de Rijn, Peter K. Sorger, Scott A. Armstrong, George D. Demetri, Sandro Santagata
Summary: This study investigates the impact of differential expression of core and accessory transcription factors on clinical outcomes in GIST, revealing that HAND1 and BARX1 expression can serve as superior predictors of relapse-free survival and predict progression-free survival on imatinib in GIST patients.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Shreyaskumar R. Patel, Peter Reichardt
Summary: In the past 20 years, significant progress has been made in the treatment of patients with GISTs using tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib, and regorafenib. The recent approvals of ripretinib and avapritinib have further expanded treatment options for patients.
Article
Biochemistry & Molecular Biology
Hyunho Yoon, Chih-Min Tang, Sudeep Banerjee, Mayra Yebra, Sangkyu Noh, Adam M. Burgoyne, Jorge De la Torre, Martina De Siena, Mengyuan Liu, Lillian R. Klug, Yoon Young Choi, Mojgan Hosseini, Antonio L. Delgado, Zhiyong Wang, Randall P. French, Andrew Lowy, Ronald P. DeMatteo, Michael C. Heinrich, Alfredo A. Molinolo, J. Silvio Gutkind, Olivier Harismendy, Jason K. Sicklick
Summary: This study identified a paracrine signaling network in the tumor microenvironment where cancer-associated fibroblasts drive GIST growth and metastasis through the production of PDGFC. Targeting CAFs with a dual PI3K/mTOR inhibitor synergized with imatinib to increase tumor cell killing. This new cellular target for GIST therapy may improve disease control and cure rates.
Review
Pharmacology & Pharmacy
Homma M. Khosroyani, Lillian R. Klug, Michael C. Heinrich
Summary: Prior to the early 2000s, patients with advanced GIST had poor prognoses due to lack of effective therapies. Tyrosine kinase inhibitors significantly improved the overall survival for these patients. This review discusses the studies that led to the approval of specific targeted therapies for different molecular subtypes of GIST, as well as their impact on future therapeutic approaches.
Article
Oncology
Rachel K. Voss, Nader N. Massarweh, Yi-Ju Chiang, Neeta Somaiah, Barry W. Feig, Christina L. Roland
Summary: Imatinib reduces recurrence risk and improves overall survival in localized GISTs, but many patients in the US do not receive guideline-concordant treatment. Factors associated with undertreatment in high-risk GIST patients include age, race, and treatment program type, while factors associated with overtreatment in low-risk patients include tumor characteristics. Guideline-concordant therapy is associated with improved survival in high-risk GIST patients, but not in low-risk patients. Further research is needed to understand the reasons for non-concordant treatment.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Review
Gastroenterology & Hepatology
Mindy X. Wang, Catherine Devine, Nicole Segaran, Dhakshinamoorthy Ganeshan
Summary: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract, primarily originating from the stomach and small intestine. They are mainly driven by activating mutations in receptor protein tyrosine kinases, allowing for prediction of patient prognosis and treatment response through mutational analysis. Clinical presentations vary and imaging plays a crucial role in diagnosis and management, with surgical resection being the preferred management for small GISTs and tyrosine kinase inhibitors serving as crucial targeted therapies for locally advanced and metastatic GISTs.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Oncology
Ping Chi, Li-Xuan Qin, Bastien Nguyen, Ciara M. Kelly, Sandra P. D'Angelo, Mark A. Dickson, Mrinal M. Gounder, Mary L. Keohan, Sujana Movva, Benjamin A. Nacev, Evan Rosenbaum, Katherine A. Thornton, Aimee M. Crago, Sam Yoon, Gary Ulaner, Randy Yeh, Moriah Martindale, Haley T. Phelan, Matthew D. Biniakewitz, Sarah Warda, Cindy J. Lee, Michael F. Berger, Nikolaus D. Schultz, Samuel Singer, Sinchun Hwang, Yu Chen, Cristina R. Antonescu, William D. Tap
Summary: This study demonstrates that the combination of imatinib and binimetinib shows efficacy and manageable toxicity in the first-line treatment of GIST.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
