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Gastrointestinal stromal tumors (GISTs) are rare soft tissue sarcomas of the gastrointestinal tract, with most carrying conserved driver mutations in the tyrosine kinase receptors KIT or PDGFRα. The use of targeted therapy against these mutations in GISTs is one of the most successful examples of precision medicine in solid tumors, beginning in 2002 with the development of imatinib, a small molecule tyrosine kinase inhibitor (TKI) of KIT. In recent years, much progress has been made in understanding the molecular mechanisms of GISTs while unveiling their genetic heterogeneity. Since development of secondary mutations leads to imatinib resistance, the majority of research efforts have focused on identification of novel inhibitors to improve outcomes in imatinib-resistant GISTs. Sunitinib and regorafenib are two TKIs with demonstrated activity after failure of imatinib, which led to the U.S. FDA approval. Pivotal phase 3 clinical trials are ongoing with two novel agents, avapritinib and ripretinib, based on their remarkable activities in the 4th or greater line settings in phase 1/2 studies of these drugs. In this review, we will outline the remarkable diversity of genetic mutations in GISTs, and review the evidence for treatment options of genomic medicine in locally advanced or metastatic gastrointestinal stromal tumors.
This article was published in the following journal.
Name: Discovery medicine
To develop and validate radiomic prediction models using contrast-enhanced computed tomography (CE-CT) to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors (GISTs).
Adenocarcinoma coexists with adjacent microscopic gastrointestinal stromal tumor (micro-GIST) is rare, especially in the rectum, where the gastrointestinal stromal tumors (GISTs) have the lower incide...
Gastrointestinal stromal tumors are the most common mesenchymal tumors of gastrointestinal tract originating from the interstitial cell of Cajal. The presentation is variable depending on the size and...
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal (GI) tract. Management of GIST patients is now based on the clinicopathological features and...
Small intestine stromal tumors (SISTs) are a type of gastrointestinal stromal tumor (GIST) that has an insidious onset. Natural orifice specimen extraction (NOSE) surgery has been gradually developed ...
Open-label, multicenter study of imatinib (400mg/die p.o.)in patients with advanced gastrointestinal stromal tumors. Patients will be treated for up to 12 months. Data regarding its best c...
The objective of this study is to compare the clinical outcomes following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive ca...
The purpose of this multicenter, single-arm, exact binomial single-stage, phase II trial is to evaluate the efficacy of Nilotinib in patients with unresectable or metastatic gastrointestin...
RATIONALE: SU011248 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. It is not yet known if SU011248 is effective in treating malignant gastrointestin...
This is a retrospective medical record abstraction to evaluate the patterns of care for Gastrointestinal stromal tumors (GIST) in the community setting. Patient demographics and character...
Neoplasms of the endometrial stroma that sometimes involve the MYOMETRIUM. These tumors contain cells that may closely or remotely resemble the normal stromal cells. Endometrial stromal neoplasms are divided into three categories: (1) benign stromal nodules; (2) low-grade stromal sarcoma, or endolymphatic stromal myosis; and (3) malignant endometrial stromal sarcoma (SARCOMA, ENDOMETRIAL STROMAL).
All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).
Neoplasms derived from the primitive sex cord or gonadal stromal cells of the embryonic GONADS. They are classified by their presumed histogenesis and differentiation. From the sex cord, there are SERTOLI CELL TUMOR and GRANULOSA CELL TUMOR; from the gonadal stroma, LEYDIG CELL TUMOR and THECOMA. These tumors may be identified in either the OVARY or the TESTIS.
A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.
Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.
Clinical trials are a set of procedures in medical research conducted to allow safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g...