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Recent advances and novel agents for gastrointestinal stromal tumor (GIST).

Lamba G, Ambrale S, Lee B, Gupta R, Rafiyath SM, Liu D - J Hematol Oncol (2012)

Bottom Line: The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone.Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative.GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic "driver" pathways, leading to dramatically improved clinical outcomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Oncology/Hematology, New York Medical College and Westchester Medical Center, Valhalla, NY 10595, USA.

ABSTRACT
The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone. Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative. GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic "driver" pathways, leading to dramatically improved clinical outcomes. A series of investigations and trials are underway to develop novel and effective ways to treat patients with GIST. In this review, we discuss the highlights of recent advances and novel agents for GIST therapy.

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KIT (CD117) gene structure and common mutations in gastrointestinal stromal tumor. Arrows indicate the positions of common mutations in the KIT gene.
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Figure 2: KIT (CD117) gene structure and common mutations in gastrointestinal stromal tumor. Arrows indicate the positions of common mutations in the KIT gene.

Mentions: In 1998, Hirota et al. defined the relationship between GIST and certain mutations in the KIT proto-oncogene that conferred uncontrolled activation to the KIT signaling enzyme [4]. Importantly, almost all GIST lesions with mutant KIT demonstrate only a single site of mutation in the KIT gene (Figure 2). Complex genetic changes are rare at initial diagnosis. Gain-of-function mutations have been recognized most commonly (up to 70% of cases) in exon 11 of KIT. Approximately 15% of GIST patients do not demonstrate activation and aberrant signaling of the KIT receptor. An additional 10% harbor mutations in the platelet-derived growth factor receptor – alpha (PDGFRA) [5,6]. Very rare cases may have mutations in the BRAF kinase [7,8]. Overall, about 5% of GISTs have no detectable kinase mutations (and are often referred to as wild type GIST). Janeway and colleagues have also shown that germline mutation in succinate dehydrogenase subunits B, C or D can cause KIT-/PDGFRA- wild type GIST [9].


Recent advances and novel agents for gastrointestinal stromal tumor (GIST).

Lamba G, Ambrale S, Lee B, Gupta R, Rafiyath SM, Liu D - J Hematol Oncol (2012)

KIT (CD117) gene structure and common mutations in gastrointestinal stromal tumor. Arrows indicate the positions of common mutations in the KIT gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3405472&req=5

Figure 2: KIT (CD117) gene structure and common mutations in gastrointestinal stromal tumor. Arrows indicate the positions of common mutations in the KIT gene.
Mentions: In 1998, Hirota et al. defined the relationship between GIST and certain mutations in the KIT proto-oncogene that conferred uncontrolled activation to the KIT signaling enzyme [4]. Importantly, almost all GIST lesions with mutant KIT demonstrate only a single site of mutation in the KIT gene (Figure 2). Complex genetic changes are rare at initial diagnosis. Gain-of-function mutations have been recognized most commonly (up to 70% of cases) in exon 11 of KIT. Approximately 15% of GIST patients do not demonstrate activation and aberrant signaling of the KIT receptor. An additional 10% harbor mutations in the platelet-derived growth factor receptor – alpha (PDGFRA) [5,6]. Very rare cases may have mutations in the BRAF kinase [7,8]. Overall, about 5% of GISTs have no detectable kinase mutations (and are often referred to as wild type GIST). Janeway and colleagues have also shown that germline mutation in succinate dehydrogenase subunits B, C or D can cause KIT-/PDGFRA- wild type GIST [9].

Bottom Line: The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone.Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative.GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic "driver" pathways, leading to dramatically improved clinical outcomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Oncology/Hematology, New York Medical College and Westchester Medical Center, Valhalla, NY 10595, USA.

ABSTRACT
The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone. Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative. GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic "driver" pathways, leading to dramatically improved clinical outcomes. A series of investigations and trials are underway to develop novel and effective ways to treat patients with GIST. In this review, we discuss the highlights of recent advances and novel agents for GIST therapy.

Show MeSH
Related in: MedlinePlus