Article
Pathology
David J. Papke, Erna Forgo, Gregory W. Charville, Jason L. Hornick
Summary: PDGFRA IHC is highly sensitive and moderately specific for PDGFRA-mutant GISTs, and can be used to triage epithelioid GISTs for optimal therapy.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Review
Oncology
Sebastian Bauer, Suzanne George, Margaret von Mehren, Michael C. C. Heinrich
Summary: While traditional GIST treatments target specific kinase mutations, resistance to these therapies is common, leading to the development of next-generation TKIs with broader therapeutic options.
FRONTIERS IN ONCOLOGY
(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
Oncology
Grazia Palomba, Panagiotis Paliogiannis, Maria C. Sini, Maria Colombino, Milena Casula, Antonella Manca, Marina Pisano, Giovanni Sotgiu, Valentina Doneddu, Giuseppe Palmieri, Antonio Cossu
Summary: This study investigated the molecular characteristics of GIST in a cohort of Sardinian patients in Italy. The majority of patients had mutations in the KIT or PDGFRa genes, with KIT mutations being more common than PDGFRa mutations. There was no significant difference in survival between mutated and wild-type cases, or between cases with KIT mutations and PDGFRa mutations.
EUROPEAN JOURNAL OF CANCER PREVENTION
(2021)
Article
Veterinary Sciences
Maria Morini, Fabio Gentilini, Maria Elena Turba, Francesca Gobbo, Luciana Mandrioli, Giuliano Bettini
Summary: This study found mutations in c-KIT and PDGFRA in canine gastrointestinal stromal tumors, and suggests an association of c-KIT mutation with a more aggressive biological behavior of the tumor.
VETERINARY SCIENCES
(2022)
Editorial Material
Oncology
Alessandro Rizzo, Maria Abbondanza Pantaleo, Annalisa Astolfi, Valentina Indio, Margherita Nannini
Summary: The D842V mutation in PDGFRA is the most common mutation in GIST, conferring primary resistance to conventional treatments. In recent years, new specific inhibitors have been developed for this mutation with promising results in clinical settings.
Review
Oncology
Heikki Joensuu
Summary: Gastrointestinal stromal tumor (GIST) is a common sarcoma arising from the gastrointestinal tract, mainly the stomach, with varying malignancy potential. Surgery is generally curative for localized GISTs. Adjuvant imatinib has been shown to improve recurrence-free survival and overall survival (OS) in high-risk GIST patients with an imatinib-sensitive mutation.
Article
Oncology
Li Liang, Xin Li, Dong Li, Ping Liu, Lin Nong, Ying Dong, Jumei Liu, Sixia Huang, Ting Li
Summary: This study found that certain clinicopathological parameters were significantly associated with relapse-free survival in GIST patients, including male gender, non-gastric tumor origin, larger tumor size, high mitotic activity, necrosis, and epithelioid morphology. KIT deletion involving codons 557/558/559, non-gastric origin, and high WHO grade were independent indicators of RFS.
Article
Pathology
Wen Huang, Wei Yuan, Lei Ren, Huaiyu Liang, Xiangyang Du, Xiangfei Sun, Yong Fang, Xiaodong Gao, Min Fu, Yihong Sun, Kuntang Shen, Yingyong Hou
Summary: The study found that PDGFRA mutant GIST mainly originates from the stomach with a relatively indolent behavior. D842V mutation and loss of CD34 expression are adverse prognostic factors. Avapritinib can effectively control advanced patients for a certain period of time.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Gastroenterology & Hepatology
Haruhiko Cho, Toshirou Nishida, Tsuyoshi Takahashi, Toru Masuzawa, Seiichi Hirota
Summary: The study found that different types of KIT gene mutations are associated with the prognosis of GIST patients, with deletions and deletion-insertion mutations clearly linked to worse survival outcomes, while duplications and substitution mutations are associated with better survival.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2022)
Article
Oncology
Sergei Boichuk, Pavel Dunaev, Vera Skripova, Aigul Galembikova, Firyuza Bikinieva, Elena Shagimardanova, Guzel Gazizova, Ruslan Deviatiiarov, Elena Valeeva, Ekaterina Mikheeva, Maria Vasilyeva, Pavel Kopnin, Vladimir Strelnikov, Ramziya Kiyamova
Summary: This study demonstrates that inhibition of KIT signaling in IM-resistant GISTs activates the FGFR signaling pathway and renders cancer cells highly sensitive to pan-FGFR inhibitors. The findings suggest that combining FGFR inhibitors with IM can be an effective therapeutic strategy for IM-resistant GIST patients.
Article
Oncology
Ying Wu, Beibei Gao, Qin Xia, Yili Zhu, Na Wang, Xiaona Chang, Bo Huang, Danju Luo, Jiwei Zhang, Peng Zhang, Heshui Shi, Jun Fan, Xiu Nie
Summary: ALK expression was detected in 7.7% of PDGFRA-mutant GISTs, indicating the importance of molecular testing to exclude the possibility of PDGFRA-mutant GISTs when encountering ALK-positive mesenchymal tumors with CD117-negative or weakly positive immunohistochemical staining.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Lei Cao, Kunming Zheng, Yanhong Liu, Peng Song, Chuntao Wang, Hongzhi Wang, Nan Wang, Shiwu Zhang, Yongjie Zhao
Summary: This study identified 897 differentially expressed genes (DEGs) between imatinib-sensitive and imatinib-resistant cell lines of GIST using RNA sequencing. Among the DEGs, 10 top genes (NDN, FABP4, COL4A1, COLEC11, MEG3, EPHA3, EDN3, LMO3, RGS4, and CRISP2) were selected and their expression trends in different imatinib-resistant cell lines were confirmed using RT-PCR. These findings suggest that these genes may potentially play a role in the clinical diagnosis and treatment of imatinib resistance in GIST.
FRONTIERS IN GENETICS
(2022)
Review
Oncology
Xiangchen Hu, Zhe Wang, Peng Su, Qiqi Zhang, Youwei Kou
Summary: This review discusses and summarizes the research on the mechanisms of secondary resistance to Imatinib Mesylate (IM) in Gastrointestinal Stromal Tumors (GISTs) conducted in the last 5 years, focusing on abnormal energy metabolism, gene mutations, non-coding RNA, and key proteins. The study found that different drug-resistance mechanism networks are closely linked and interconnected, and the combined inhibition of these mechanisms could potentially become new therapeutic options for GIST treatment. Implementing individualized therapies based on the identification of resistance mechanisms may also provide new adjuvant treatment options for IM-resistant GISTs, delaying the progression of the disease.
FRONTIERS IN ONCOLOGY
(2022)