AI Article Synopsis
- Tyrosine kinase inhibitors (TKIs) are essential for treating advanced gastrointestinal stromal tumors (GIST), with new compounds developed to combat resistance due to mutations in KIT and PDGFRα.
- Recent studies have highlighted TKIs like ripretinib, avapritinib, and crenolanib as having significant efficacy in both preclinical and clinical settings, with ripretinib setting a new standard for fourth-line treatment.
- The landscape of GIST treatment is expanding with the potential addition of other agents such as MEK inhibitors, immunotherapy, and TRK-targeted therapy for specific patient subsets.
Article Abstract
Purpose Of Review: Tyrosine kinase inhibitors (TKIs) are the backbone for advanced gastrointestinal stromal tumor (GIST) treatment. The increasing knowledge concerning the structure and the changing conformational status because of some mutations in KIT and PDGFRα, allowed the development of new efficient compounds, with the main goal to overcome resistance in GIST. This review summarizes the latest developments in the treatment of GIST patients.
Recent Findings: Amongst the several TKIs currently being studied in GIST, ripretinib, avapritinib and crenolanib had shown promising potent activity in preclinical studies and clinical trials. Ripretinib is a type II inhibitor that exerts its main action in the switch pocket of the activation loop, by mimicking the inhibition exerted by the regulatory region in this domain. Ripretinib is considered the new standard in the fourth line in advanced GIST. Avapritinib is a type I inhibitor synthesized to exerts its activity in the active conformation of the activation loop of KIT and PDFGRα. The relevant activity reported with avapritinib in patients carrying the D842 v mutation represents, for first time, an active therapeutic option in this resistant mutant. Crenolanib is a type I selective inhibitor of PDGFRα-resistant mutants, mainly D842 V, which is currently under clinical trial.
Summary: New potent TKIs are being approved, adding value to the already three registered drugs. Other agents, such as MEK inhibitors, immunotherapy and TRK-targeted therapy are potential new options in specific subsets of GIST patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/CCO.0000000000000642 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Defining Textbook Outcomes for Minimally Invasive Surgical Resection of Small Gastrointestinal Stromal Tumors (GIST) of the Stomach.
Ann Surg Oncol
January 2025
Department of Surgery, University of California San Diego School of Medicine, San Diego, CA, USA.
Background: Textbook outcome (TO) has been utilized to assess the quality of surgical care. This study aimed to define TO rates for minimally invasive gastric gastrointestinal stromal tumor (GIST) resections in a bi-institutional cohort.
Methods: Patients with gastric GIST (≤ 5 cm) who underwent laparoscopic or robotic resection (January 2014 to January 2024) were retrospectively identified from two GIST centers.
Long non-coding RNA MSC-AS1 confers imatinib resistance of gastrointestinal stromal tumor cells by activating FNDC1 and ANLN-mediated PI3K/AKT pathway.
Hum Cell
January 2025
Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Sendai Street, Nanguan District, Changchun, 130031, China.
Imatinib resistance is a major obstacle to the successful treatment of gastrointestinal stromal tumors (GIST). Long non-coding RNAs (LncRNAs) have been identified as important regulatory factors in chemotherapy resistance. This study aimed to identify key lncRNAs involved in imatinib resistance of GISTs.
View Article and Find Full Text PDFIdentifying subtle differences : a radiomics model assessment for gastric schwannomas and gastrointestinal stromal tumors across risk grades.
Front Oncol
December 2024
Department of Computed Tomography and Magnetic Resonance, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Objective: This study aims to develop and validate an enhanced computed tomography (CT)-based radiomics model to differentiate gastric schwannomas (GS) from gastrointestinal stromal tumors (GIST) across various risk categories.
Methods: This retrospective analysis was conducted on 26 GS and 82 GIST cases, all confirmed by postoperative pathology. Data was divided into training and validation cohorts at a 7:3 ratio.
Prediction of Ki-67 expression in gastric gastrointestinal stromal tumors using histogram analysis of monochromatic and iodine images derived from spectral CT.
Cancer Imaging
December 2024
Department of Radiology, Lanzhou University Second Hospital, Cuiyingmen No.82, Chengguan District, Lanzhou, 730030, People's Republic of China.
Purpose: To assess and compare the diagnostic efficiency of histogram analysis of monochromatic and iodine images derived from spectral CT in predicting Ki-67 expression in gastric gastrointestinal stromal tumors (gGIST).
Methods: Sixty-five patients with gGIST who underwent spectral CT were divided into a low-level Ki-67 expression group (LEG, Ki-67 < 10%, n = 33) and a high-level Ki-67 expression group (HEG, Ki-67 ≥ 10%, n = 32). Conventional CT features were extracted and compared.
Low-dose Imatinib Efficacy in a Gastrointestinal Stromal Tumor Patient With Exon 11 W557_K558 Deletion.
In Vivo
December 2024
Department of Medical Oncology, Hyogo Cancer Center, Akashi, Japan.
Background/aim: Gastrointestinal stromal tumors (GISTs) are rare cancers originating from Cajal's stromal cells in the gastrointestinal tract. The most common driver mutation in these cancers is the KIT mutation. This report presents a case of response to low-dose imatinib in a patient with GIST harboring KIT exon 11 W557_K558 deletion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!