• Gastrointestinal stromal tumor
• Metastatic liver tumor
• Sigmoid colon cancer

• Associated
• Gastrointestinal stromal tumor
• Neoplasia
• Secondary
• Tumor

• Disease Progression
• Gastrointestinal Neoplasms/epidemiology
• Gastrointestinal Neoplasms/pathology
• Gastrointestinal Stromal Tumors/epidemiology
• Gastrointestinal Stromal Tumors/pathology
• Humans
• Incidence
• Mass Screening
• Neoplasms, Multiple Primary/epidemiology
• Neoplasms, Multiple Primary/pathology
• Neoplasms, Multiple Primary/prevention & control
• Neoplasms, Second Primary/epidemiology
• Neoplasms, Second Primary/pathology
• Neoplasms, Second Primary/prevention & control
• Risk Factors

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet-derived growth factor receptor α (PDGFRA) wild-type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild-type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology-Based Annotation System (KOBAS) online tools, respectively. Protein-protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub-networks using the Molecular Complex Detection (MCODE) plug-in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in ‘cell adhesion’, ‘biological adhesion’, ‘cell-cell signaling’, ‘PI3K-Akt signaling pathway’ and ‘ECM-receptor interaction’, while the 308 downregulated genes were predominantly involved in ‘inflammatory response’, ‘sterol metabolic process’ and ‘fatty acid metabolic process’, ‘small GTPase mediated signal transduction’, ‘cAMP signaling pathway’ and ‘proteoglycans in cancer’. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub-networks also revealed these genes were primarily involved in significant pathways, including ‘PI3K-Akt signaling pathway’, ‘proteoglycans in cancer’, ‘pathways in cancer’, ‘Rap1 signaling pathway’, ‘ECM-receptor interaction’, ‘phospholipase D signaling pathway’, ‘ras signaling pathway’ and ‘cGMP-PKG signaling pathway’. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild-type GISTs, including phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb-B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.

This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib.

Patients received oral dovitinib 500 mg day⁻¹, 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment.

Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2–66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1–11.9%), and 5.3% (n=2; 90% CI, 0.9–15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8–7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n=7), fatigue (n=5), vomiting (n=4), hypertriglyceridaemia (n=4), and γ-glutamyltransferase increase (n=4).

Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.

• Case series
• Gastrointestinal stromal tumors
• Imatinib
• Review
• Second malignancies

• Colorectal/rectal GIST
• neoadjuvant/adjuvant imatinib
• prognostic factors

Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries.

• Gastrointestinal stromal tumors
• carcinoid
• lymphoma