Targeting FGFR inhibition in cholangiocarcinoma

Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which are often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications have been identified in almost half of CCAs, in particular in intrahepatic CCA (iCCA), the subtype arising from bile ducts within the liver. Among patients with CCA, fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur almost exclusively in iCCA, where they are estimated to be found in up to 10–15% of patients. Clinical trials for selective FGFR kinase inhibitors have shown consistent activity of these agents in previously treated patients with iCCA harbouring FGFR alterations. Current FGFR kinase inhibitors show differences in their structure, mechanisms of target engagement, and specificities for FGFR1, 2, 3 and 4 and other related kinases. These agents offer the potential to improve outcomes in FGFR-driven CCA, and the impact of variations in the molecular profiles of the FGFR inhibitors on efficacy, safety, acquired resistance mechanisms, and patients’ health-related quality of life remains to be fully characterized. The most common adverse event associated with FGFR inhibitors is hyperphosphatemia, an on-target off-tumour effect of FGFR1 inhibition, and strategies to manage this include dose adjustment, chelators, and the use of a low phosphate diet. As FGFR inhibitors and other targeted agents enter the clinic for use in FGFR-driven CCA, molecular testing for actionable mutations and monitoring for the emergence of acquired resistance will be essential

The implications of the genre-based approach on the teaching of English writing at the Department of Foreign Languages, Khon Kaen University in north-eastern Thailand

University of Technology, Sydney. Faculty of Education.The Thai government has proposed education reform programs to be competitive with its neighbours and globally. One major policy is to improve competency in English. Thailand has a long history of importing approaches for teaching English from western countries. For a complex variety of reasons the structural-based approaches have been the most influential ones on both teachers and bureaucrats. While these approaches enable Thais to communicate at the basic level, emphasising spoken language, they do not provide systematic guidance to write extended texts effectively. Thai educators have tended to import approaches literally without adequately researching the practicality and suitability of them. This thesis is an attempt to explore whether it is possible to adapt a recently evolved, western 'genre-based' approach to the teaching of English in Thailand. The research focuses on factual English writing because it is highly valued in government, commerce and industry. English and Thai rhetorical patterns differ significantly so students need to write their texts to meet English readers' expectations. To achieve this, students need to be taught to write explicitly. Soundly based in Systemic Functional Linguistic theory, the genre-based approach teaches writing at whole text, paragraph and clause levels. It is concerned with realising appropriate generic structure for the different social communication tasks. This approach has the potential to improve Thai students' writing ability. The research project was primarily an ethnographic-case study that was carried out with the co-operation of 45 third year English major students for 14 weeks (from October, 1997 to February, 1998) at the Department of Foreign Languages, Khon Kaen University in northeast Thailand. It is centred on the Exposition genre because some Thai educators had noted that it was one of the most neglected in the Thai educational system, but one of the most valuable genres in western culture. The research outcomes showed that the genre-based approach had a significant positive impact on students' factual writing, showing gains in the control of generic structure and language features of the Exposition. Nevertheless, the research suggests that for the genre-based approach to be successfully implemented in a foreign language context such as Thai, a number of modifications are necessary. The genre-based approach provides students with insights into cultural expectations of writing in English and has the potential to contribute to the policy goals of the Thai government for the upgrading of English teaching and also contribute to its wish of achieving the education refonn agenda