Gastrointestinal stromal tumor最新文献

{"title":"A narrative review of imatinib-resistant gastrointestinal stromal tumors.","authors":"Yujiro Hayashi, Vy Truong Thuy Nguyen","doi":"10.21037/gist-21-10","DOIUrl":"10.21037/gist-21-10","url":null,"abstract":"<p><strong>Objective: </strong>Review the studies that investigate the mechanisms underlying imatinib-resistant gastrointestinal stromal tumors (GIST).</p><p><strong>Background: </strong>GIST are the most common mesenchymal tumors of the gastrointestinal (GI) tract and the most common sarcoma in humans. GIST are thought to be arise from interstitial cells of Cajal (ICC), pacemaker and neuromodulator cells in the GI tract, as well as \"fibroblast\"-like cells, which are another type of interstitial cells of the gut wall and also known as telocyte or platelet-derived growth factor-alpha (PDGFRA)-positive cells. The majority of GIST harbor gain-of-function mutations in either <i>KIT</i> or <i>PDGFRA</i>, and these gain-of-function mutations are mutually exclusive and most often heterozygous. GIST are responsive to the KIT/PDGFRA tyrosine kinase inhibitor (TKI), imatinib, the standard first-line drug for advanced and metastatic GIST. However, imatinib alone does not eradicate GIST despite an initial clinical benefit, and more than 90% of GIST harbor imatinib-resistance. Although second and third-generation TKIs have been developed and are currently in clinical use, they are not curative for refractory and metastatic GIST due to the emergence of clones with drug-resistant mutations. Eradication of drug-resistant GIST will cure patients with refractory GIST. Several mechanisms may contribute to refractory GIST. These mechanisms are secondary mutations in <i>KIT</i> and/or <i>PDGFRA</i>, alternative activation of tyrosine kinases, stem cells for GIST and cellular quiescence, a reversible nonproliferating state in which cells retain the ability to reenter cell proliferation.</p><p><strong>Methods: </strong>We review our current optimal treatment approach for managing patients with advanced and refractory GIST.</p><p><strong>Conclusions: </strong>This review explores the novel and potential therapeutic approaches to combat drug-resistant GIST.</p>","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/d7/nihms-1767211.PMC9268655.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40491466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review of surgical management of gastrointestinal stromal tumors","authors":"I. Kalinowska, M. Zdzienicki, J. Skoczylas, P. Rutkowski","doi":"10.21037/gist-21-2","DOIUrl":"https://doi.org/10.21037/gist-21-2","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48319762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant therapy for primary GIST: is longer really better? A narrative review","authors":"Pamela W. Lu, C. Raut","doi":"10.21037/gist-21-4","DOIUrl":"https://doi.org/10.21037/gist-21-4","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41439537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design your strategy, define your costs: third or subsequent-lines in advanced gastrointestinal stromal tumors (GIST)","authors":"J. Giuliani","doi":"10.21037/gist-21-5","DOIUrl":"https://doi.org/10.21037/gist-21-5","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48985492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ripretinib—a new star in the firmament","authors":"A. Kollár","doi":"10.21037/GIST-21-3","DOIUrl":"https://doi.org/10.21037/GIST-21-3","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43594346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose escalation of ripretinib can lead to response in advanced gastrointestinal stromal tumor patients refractory to the standard dose: a report of two cases","authors":"P. A. Costa, Caroline Hana, N. Balaji, A. Skryd, Brianna Nicole Valdes, R. Minjares, Priscila Barreto-Coelho, Andrea P Espejo-Freire, Muhammad Hakim, Emily E. Jonczak, T. Subhawong, A. Livingstone, J. Trent, G. D'Amato","doi":"10.21037/GIST-21-1","DOIUrl":"https://doi.org/10.21037/GIST-21-1","url":null,"abstract":"Despite an initial response, most metastatic gastrointestinal stromal tumor (GIST) patients will ultimately be refractory to all current therapies, including imatinib, sunitinib, and regorafenib. Ripretinib at 150 mg daily was recently approved as an additional line of treatment. Few options remain after ripretinib. Here we report two cases with responses to dose escalation of ripretinib after progressing on the standard dose. Case 1: A 25-year-old man was diagnosed with a kit exon 9 mutated small intestine GIST after presenting with abdominal pain. The tumor was resected, but a year later, he developed metastases to the liver and pelvis. Over the course of three years, he received multiple lines of therapies as his disease progressed, including imatinib, sunitinib, and regorafenib. He was then placed on ripretinib 150 mg daily. However, he had disease progression after two months. Ripretinib was increased to 150 mg twice a day, which he tolerated well. After three months, he had regression of his disease. Case 2: A 54-year-old male was diagnosed with an unresectable kit exon 11 mutated gastric GISTs after presenting with abdominal pain. Imatinib led to an 80% regression, allowing surgical excision. A year later, his disease recurred. Over the course of 5 years, due to multiple recurrences, he received two additional surgeries, with imatinib, sunitinib, regorafenib, and avapritinib on either the adjuvant or neoadjuvant setting. Ultimately, he developed a metastatic GIST to the left suprarenal region, retroperitoneum, and epigastric region. He was then started on ripretinib 150 mg daily, experiencing progression of his disease in three months. Ripretinib was escalated to 150 mg twice a day, which he tolerated well, and after three months, he had a regression. Dose escalation of ripretinib leads to response in patients that progressed after the standard dose, and it is well-tolerated, being a promising new treatment option in advanced GIST.","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47100488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avapritinib—a therapeutic breakthrough for PDGFRA D842V mutated gastrointestinal stromal tumors","authors":"Evelyne Roets, N. Steeghs","doi":"10.21037/gist-22-7","DOIUrl":"https://doi.org/10.21037/gist-22-7","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44052706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The past, present, and future: the evolving role and challenges of surgery in the multimodal management of gastrointestinal stromal tumors","authors":"R. Witt, Heather G Lyu, E. Keung","doi":"10.21037/gist-22-10","DOIUrl":"https://doi.org/10.21037/gist-22-10","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44106074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resection of a giant gastrointestinal stromal tumor after failed imatinib treatment during the COVID-19 pandemic: a case report","authors":"Katie Yusun Kwon, F. Iriarte, H. Hartman, Juhi Mittal, A. Di Carlo, A. Abbas","doi":"10.21037/gist-21-12","DOIUrl":"https://doi.org/10.21037/gist-21-12","url":null,"abstract":"","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47533971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dawn of immunotherapy treatment for gastrointestinal stromal tumors","authors":"S. Schuetze","doi":"10.21037/gist-22-4","DOIUrl":"https://doi.org/10.21037/gist-22-4","url":null,"abstract":"© Gastrointestinal Stromal Tumor. All rights reserved. Gastrointest Stromal Tumor 2022 | https://dx.doi.org/10.21037/gist-22-4 Gastrointestinal stromal tumors (GIST) are characterized by pathogenic activating mutations in tyrosine kinases, or less commonly by loss of succinate dehydrogenase (SDH) complex activity through epigenetic silencing or loss of function mutation in one of the SDH subunits (1). A large majority of GIST contain activating mutations in KIT or platelet-derived growth factor receptor-alpha (PDGFRA) which are generally mutually exclusive. Very rarely, loss of neurofibromin-1, activation of RAS, translocation of neurotrophic receptor tyrosine kinase (NTRK) or cryptic genomic changes lead to development of GIST. A recent study suggests that spindle cell neoplasms of the gastrointestinal tract harboring translocations involving NTRK are distinct from GIST, and these malignancies respond to treatment with inhibitors of NTRK activity (2). The development of orally bioavailable small molecule inhibitors of KIT and PDGFRA substantively changed the treatment and survival of patients with locally advanced or metastatic GIST extending medial survival from less than 2 to more than 4 years with about 25% of patients surviving more than 10 years after the start of imatinib (3-5). However, secondary mutations in KIT or PDGFRA leading to resistance to kinase inhibition develop in many patients, and a minority have mutations in GIST that render primary resistance to imatinib. Once resistance to imatinib develops, the tumor progression-free interval generally is much shorter than with initial imatinib therapy (6-8). Moreover, SDH-deficient GISTs are resistant to treatment with imatinib although a minority may respond to treatment with sunitinib or other vascular growth factor receptor inhibitors. Few formal trials of non-tyrosine kinase inhibitor (TKIs) chemotherapy in treatment of advanced GIST have been conducted, but data collected prior to widespread incorporation of TKIs into the treatment of GIST suggests that GIST is resistant to conventional chemotherapy such as DNA-damaging agents (9,10). Thus, there is strong interest in developing alternative treatments for GIST in combination with TKIs in sensitive tumors, or in place of TKIs in resistant tumors. Much has been written about preclinical studies and biomarker analyses that suggests a role for immunotherapy in management of GIST (11-13). However, we are in the dawn of immunotherapy for GIST, and much needs to be learned to translate our understanding of GIST immunobiology into standard clinical care. A pilot study of imatinib combined with interferon-α2b in patients with imatinib-naïve GIST showed objective partial response in all patients treated (N=8); but, to my knowledge, a larger trial to confirm the high response rate has not been conducted (14). A pilot trial of lowdose metronomic oral cyclophosphamide combined with pembrolizumab in 10 patients with GIST produced no objective re","PeriodicalId":93755,"journal":{"name":"Gastrointestinal stromal tumor","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45658151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}