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Overview of Therapeutic Biomarkers in Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Sherry X. Yang, Janet E. Dancey Treatment
c-Kit or CD117, encoded by the KIT gene, is a cytokine receptor expressed on the cell membrane of hematopoietic stem cells and other cell types (Chapter 9). Mutations in the KIT gene and PDGFRA are found in about 85% and 10% of gastrointestinal stromal tumors (GIST), respectively, and some in other types of tumors. Imatinib is indicated for patients with KIT-positive unresectable and/or metastatic malignant GIST as well as adjuvant therapy of adult patients after resection of KIT-positive GIST [38]. The mutations-negative GIST tumors are in general resistant to imatinib therapy. In early 2020, the FDA approved avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations. It is the first therapy approved for patients with unresectable and metastatic malignant GIST harboring a PDGFRA exon 18 mutation.
Tumor Markers
Published in Paloma Tejero, Hernán Pinto, Aesthetic Treatments for the Oncology Patient, 2020
In gastrointestinal stromal tumors (GISTs), the determination of the Kit CD117 protein is routine practice, but of use only for diagnosis. The analysis of the c-Kit and PDGFRA gene mutations has a response-predictive value to treatment with targeted therapies (imatinib or sunitinib) as well as a prognostic value [19].
Metastatic Gastrointestinal Stromal Tumor with Bleeding
Published in Savio George Barreto, Shailesh V. Shrikhande, Dilemmas in Abdominal Surgery, 2020
Inian Samarasam, K. Senthilnathan
Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the gastrointestinal tract. They can occur anywhere in the gastrointestinal tract though most commonly in the stomach (60%) followed by the small intestine (30%) [1]. First described in the year 1983, these tumors originate from interstitial cells of Cajal (pacemaker cells), located within the myenteric plexus. The tumor cells express a tyrosine kinase receptor encoded by the oncogene KIT2. Immunohistochemical marker CD117 (c-kit) codes for the KIT protein and has been helpful in distinguishing gastrointestinal stromal tumors from other mesenchymal tumors. Discovered on GIST1 (DOG1) was shown by gene expression profiling to be highly expressed in gastrointestinal stromal tumors. Several recent studies have demonstrated the higher sensitivity of antibodies that recognize DOG1 in the diagnosis of a gastrointestinal stromal tumor compared with KIT.
Investigation of apoptotic and antiproliferative effects of Turkish natural tetraploids Trifolium pratense L. extract on C6 glioblastoma cells via light and electron microscopy
Published in Ultrastructural Pathology, 2023
Gamze Tanrıverdi, Aynur Abdulova, Hatice Çölgeçen, Havva Atar, Belisa Kaleci, Tuğba Ekiz-Yılmaz
Recently, Mitrofanova L et al. explained that glioblastoma consists of different type of cells like pericytes, gliomas, astrocytomas, etc. Some of these cells that are CD117 positive, are also called telocytes (Tcs).41 These unique cells are located in the neighborhood of vessels and are responsible for maintenance of tumor growth and have stem cell like properties. In addition, Mou et al. published that Tcs had contributed to typical tumor formation and promoted the proliferation of tumoral cells along with the other stromal cells.42 And also, Mirancea et al. reported that Tcs seem to promote the tumor formation to become even more invasive.43 In our study, we lost a lot of cells due to the effect of the herb, but also found out that a part of the living cells which stained with immunocytochemistry highly expressed CD117. The presence of this large number of positive cells made us think that these cells that remained unaffected or slightly affected by the drug, might actually be Telocytes. And also, while Trifolium pratense L. is effective on many other cells that are forming the glioblastoma microenvironment, its activity on CD117 positive cells is seen to be limited. As it is known, CD117 is a tyrosine kinase receptor. As a result, tyrosine kinase inhibitors like imatinib are used for treatment of gastrointestinal tumors, Ewing sarcoma and ovarian cancers that are rich in CD117 positive cells.44 When we look from this aspect, we think that Trifolium pratense L. can be more effective when used together with tyrosine kinase inhibitors like imatinib.
Emerging treatments for chronic urticaria
Published in Expert Opinion on Investigational Drugs, 2022
The receptor for stem cell factor KIT (CD117) is essential for mast cell differentiation and function. CDX-0159 is a mAb that specifically binds the extracellular dimerization domain of Kit and thereby inhibits activation of KIT by SCF. A phase 1 study demonstrated a dose-dependent, profound, and sustained suppression of plasma tryptase, indicative of decreased mast cell load/activation [67]. Interim analysis of a study (NCT04548869) investigating CDX-0159 in CINDU types (demonstrated that a single dose of intravenous CDX-0159 (3 mg/kg) resulted in a complete response in 95% of 20 patients with cold urticaria or symptomatic dermographism including patients who had received prior omalizumab. Interestingly enough, the effect was sustained for a median duration of 77 days in cold urticaria and 57 days in SD patients who completed the 12-week follow-up period [68]. CDX-0159 was generally well tolerated and no clinically significant decreases in hematology parameters were observed. The most common adverse events were hair color changes (70%), infusion reactions (45%), and taste disorders (40%) [68]. A phase 1 multiple ascending dose study of CDX-0159 as add-on therapy in CSU is recruiting (NCT04538794, estimated study completion date Dec 2021) (Table 1).
Progress in determining response to treatment in gastrointestinal stromal tumor
Published in Expert Review of Anticancer Therapy, 2020
Junaid Arshad, Jibran Ahmed, Ty Subhawong, Jonathan C Trent
GIST originates from the interstitial cells of Cajal, which share morphologic and immunophenotypic similarities with these tumors. These cells stain for vimentin and are immunoreactive for KIT (CD117) and CD34, whereas they typically lack a myoid or schwannian immunophenotype (e.g. S100) [4]. CD117 is a product of the c-kit proto-oncogene expression. On immunohistochemistry (IHC), CD117 and DOG1 (ANO1/TMEM16A) are most specific for GIST and help to differentiate these from other tumor types [5]. CD34 is positive on IHC in 70% of cases of GIST [6], varying from 47% in the small bowel to 96–100% in rectum and esophagus [7]. CD34 is, however, also expressed by cells in tumors of fibroblastic and endothelial origin. CD117, on the other hand, is expressed by 85% of cells of malignant GIST, both spindle cell and epithelioid subtypes. Other mesenchymal GI tumors (leiomyoma, leiomyosarcoma, and schwannomas) do not usually express CD117 [8]. In a small subset of tumors that are wild-type for KIT and PDGFRA, succinate dehydrogenase (SDH) may be deficient through deletion or epigenetic repression [9].