Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sunitinib, a small molecule, is a multitargeted receptor kinase inhibitor which targets the vascular endothelial growth factor receptor and platelet-derived growth factor receptor as well as several others. Initially approved for the treatment of renal cell carcinoma as well as imatinib-resistant gastrointestinal stromal tumors, the activity of sunitinib has been explored in several other solid tumors including non-small cell lung cancer (NSCLC). An initial phase II trial in 63 previously treated NSCLC patients using a dose of 50 mg daily 4 of 6 weeks showed a response rate of 11.1% and a stable disease rate of 26.8%. The median time to disease progression and overall survival was 12.0 and 23.4 weeks, respectively. The principal toxicities included fatigue, pain, myalgias, nausea/vomiting, and hypertension. Three hemorrhagic deaths were reported (two pulmonary and one central nervous system). After this trial was completed, a subsequent sequential cohort of 47 previously treated NSCLC patients were treated on a continuous dosing schedule of sunitinib at 37.5 mg daily. A response rate of 2.1% was reported with a stable disease rate of 19.X%. The median time to progression was 12.3 weeks with a median survival time of 38.1 week. Toxicities were, in general, less frequent and similar to those noted in the initial trial. Sunitinib is currently being evaluated in combination with a number of standard regimens commonly used in NSCLC as well as a maintenance drug after first-line platinum-based treatment of advanced NSCLC. Results of these trials are eagerly awaited and will help define the role of sunitinib in the therapeutic approach to NSCLC.
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PMID:The current status and evolving role of sunitinib in non-small cell lung cancer. 1852 Feb 93

About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene and occur almost absolutely in carcinomas arising in non-smokers. Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c-Met receptor kinase, has been used in the treatment of ALK-positive non-small cell lung cancer. Side effects of crizotinib mostly consist of grade 1-2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2 edema and fatigue; grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis. We are presenting a case of adenocarcinoma of lung, who progressed on first-line chemotherapy and received crizotinib as second line therapy for 9 months. Patient has very good partial response to crizotinib and had some side effects of crizotinib like nausea, vomiting, diarrhea, fatigue, asthenia and anorexia, asymptomatic transaminitis in the first 2 to 3 weeks of therapy and managed symptomatically. But after 9 months, he developed sudden onset left sided vision loss. On fundoscopic examination he was found to have "cherry red spot" and fundus flourescein angiography revealed central retinal artery occlusion (CRAO). After 15 days of vision loss patient developed pleural effusion, and pleural fluid cytology was positive for malignant cells. Visual symptoms are very well known in the literature as side effects of crizotinib, but CRAO is not yet been documented. As this patient is not having any prothrombotic state like diabetes, hypertension, atherosclerosis, hyperhomocysteinemia or any genetic disorders except malignancy. Hypercoagulability disorders are known to be commonly associated with a variety of cancer types including lung cancer. This appears to be a sign of early crizotinib resistance in this patient because there was no history of prior hypercoagulable state. To the best of our knowledge this is the first case report in the world literature, as CRAO presenting as a sign of crizotinib resistance in an adenocarcinoma of lung patient who was on crizotinib.
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PMID:Central retinal artery occlusion, an early sign of crizotinib resistance in an alk positive adenocarcinoma of lung: A rare case report. 2760 84

Here, we report a highly unusual case of high-grade glioneuronal tumor with a neurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. The tumor was diagnosed as a high-grade glioneuronal tumor, unclassified. Methylation profiling classified it as a diffuse leptomeningeal glioneuronal tumor (DLGNT) with low confidence. This tumor showed genotypes frequently found in DLGNT such as 1p/19q codeletion without IDH mutation and, however, did not have the typical DLGNT clinical and histological features. RNA sequencing identified an ARHGEF2 (encoding Rho/Rac guanine nucleotide exchange factor 2)-NTRK1 fusion gene. The presence of recurrent NTRK fusion in glioneuronal tumors has an important implication in the clinical decision making and opens up a possibility of novel targeted therapy.
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PMID:High-grade glioneuronal tumor with an ARHGEF2-NTRK1 fusion gene. 3101 18