The Controlling Cancer Summit, 17-19 May 2016, London, UK.

The Controlling Cancer Summit, London, UK, 17-19 May 2016 The Controlling Cancer Summit is an intimate informal meeting that annually gathers international academic and clinical researchers to network and debate the current advancements and challenges of oncology research. This year, it focused not only on diagnostic/prognostic biomarkers and genetic influences in cancer but also novel and sometimes unconventional therapeutic interventions. This report will summarize the meeting highlights that contribute to our comprehension of cancer biology and new innovative ways to target this disease

Advances and challenges in targeting FGFR signalling in cancer.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate numerous cellular processes. Deregulation of FGFR signalling is observed in a subset of many cancers, making activated FGFRs a highly promising potential therapeutic target supported by multiple preclinical studies. However, early-phase clinical trials have produced mixed results with FGFR-targeted cancer therapies, revealing substantial complexity to targeting aberrant FGFR signalling. In this Review, we discuss the increasing understanding of the differences between diverse mechanisms of oncogenic activation of FGFR, and the factors that determine response and resistance to FGFR targeting

Gatekeeper Mutations and Intratumoral Heterogeneity in <i>FGFR2</i>-Translocated Cholangiocarcinoma.

FGFR2 genetic translocations are frequent in cholangiocarcinoma, yet despite initial sensitivity to FGFR inhibitors in clinic, patients quickly become resistant to targeted therapies. The work published by Goyal and colleagues demonstrates that acquisition of gatekeeper mutations in FGFR2 and intratumoral heterogeneity drive resistance in patients with FGFR2-translocated intrahepatic cholangiocarcinoma, which will have important implications for management of the disease in clinic. Cancer Discov; 7(3); 248-9. ©2017 AACR.See related article by Goyal et al., p. 252

Reciprocal priming between receptor tyrosine kinases at recycling endosomes orchestrates cellular signalling outputs

From Wiley via Jisc Publications RouterHistory: received 2020-10-29, rev-recd 2021-04-27, accepted 2021-04-28, pub-electronic 2021-06-04Article version: VoRPublication status: PublishedFunder: Wellcome Trust; Grant(s): 107636/Z/15/Z, 210002/Z/17/ZFunder: UKRI | Biotechnology and Biological Sciences Research Council (BBSRC); Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/R015864/1, BB/M011208/1Funder: UKRI | Medical Research Council (MRC); Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/T016043/1Funder: Cancer Research UK (CRUK); Id: http://dx.doi.org/10.13039/501100000289; Grant(s): A27445Funder: NIHR Manchester Biomedical Research Centre; Grant(s): IS‐BRC‐1215‐20007Funder: Breast Cancer Now; Grant(s): MAN‐Q2‐Y4/5Abstract: Integration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine‐tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains poorly elucidated. Combining quantitative phosphoproteomics and targeted assays, we generated a detailed picture of recycling‐dependent fibroblast growth factor (FGF) signalling in breast cancer cells, with a focus on distinct FGF receptors (FGFRs). We discovered reciprocal priming between FGFRs and epidermal growth factor (EGF) receptor (EGFR) that is coordinated at recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR‐mediated proliferation but not cell invasion. In turn, FGFR signalling primes EGF‐mediated outputs via EGFR threonine 693 phosphorylation. This reciprocal priming between distinct families of RTKs from recycling endosomes exemplifies a novel signalling integration hub where recycling endosomes orchestrate cellular behaviour. Therefore, targeting reciprocal priming over individual receptors may improve personalized therapies in breast and other cancers

Genome-wide association studies of cancer: current insights and future perspectives.

Genome-wide association studies (GWAS) provide an agnostic approach for investigating the genetic basis of complex diseases. In oncology, GWAS of nearly all common malignancies have been performed, and over 450 genetic variants associated with increased risks have been identified. As well as revealing novel pathways important in carcinogenesis, these studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers. The clinical application of GWAS is starting to provide opportunities for drug discovery and repositioning as well as for cancer prevention. However, deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS