Fibroblast growth factor receptors in cancer: genetic alterations,diagnostics, therapeutic targets and mechanisms of resistance

Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer     

Cognition in breast cancer survivors: A pilot study of interval and continuous exercise

Objectives

The current study investigated the effects of two exercise interventions on cognitive function amongst breast cancer survivors.

The Multimedia activity recall for children and adolescents (MARCA): development and evaluation

Background  

Self-report recall questionnaires are commonly used to measure physical activity, energy expenditure and time use in children and adolescents. However, self-report questionnaires show low to moderate validity, mainly due to inaccuracies in recalling activity in terms of duration and intensity. Aside from recall errors, inaccuracies in estimating energy expenditure from self-report questionnaires are compounded by a lack of data on the energy cost of everyday activities in children and adolescents. This article describes the development of the Multimedia Activity Recall for Children and Adolescents (MARCA), a computer-delivered use-of-time instrument designed to address both the limitations of self-report recall questionnaires in children, and the lack of energy cost data in children.