NTRK gene fusions, TRK inhibitors and testing approaches BluePrint

Dr Andrea Sartore-Bianchi is head of Clinical Molecular Oncology at the Department of Hematology & Oncology, Niguarda Cancer Center, Milano, Italy. He completed his medical degree at the University of Pavia in 1999, and undertook specialist training at IRCCS Policlinico San Matteo. After completing his doctoral studies, he conducted preclinical research at the Division of Clinical Pharmacology and Experimental Cancer Therapeutics in the Department of Medicine at Brown University, Rhode Island, USA. Dr Sartore-Bianchi’s main clinical and research interests include the treatment of gastrointestinal cancers, particularly colorectal carcinomas, focusing on biomarkers of sensitivity/resistance to molecular-targeted therapies and on the epidermal growth factor receptor signal transduction pathway. He is principal and co-investigator in Phase I-II-III clinical trials for gastrointestinal malignancies, and first author of research articles in the Journal of Clinical Oncology, Cancer Research, Clinical Cancer Research and PLoS One. Currently, he is adjunct Professor for the School of Specialization in Oncology and Pharmacology at the University of Milano. He has been listed among the top 30 authors of primary research papers on cancer.

López-Ríos F, Illei PB, Rusch V, Ladanyi M. Multiple lines of evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive SV40 PCR results due to presence of SV40 sequences in common laboratory plasmids. Lancet 2004; 364: 1157-1166. Conde E, Angulo B, Tang M, Morente M, Torres-Lanzas J, López-Encuentra A, López-Ríos F, Sánchez-Céspedes M. Molecular context of the epidermal growth factor receptor mutations: evidence for the activation of mTOR/S6K signalling. Clin Cancer Res 2006; 12: 710-717. López-Ríos F, Chuai S, Flores R, Shimizu S, Ohno T, Wakahara K, Illei PB, Hussain S, Krug L, Zakowski MF, Rusch V, Olshen AB, Ladanyi M. Global gene expression profiling of pleural mesotheliomas. Overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res 2006; 66: 2970-2979. López-Ríos F, Sánchez-Aragó M, García-García E, Ortega AD, Berrendero JR, Pozo-Rodríguez F, López-Encuentra A, Ballestín C, Cuezva JM. Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of Carcinomas. Cancer Res 2007; 67: 9013-9017. Angulo B, Suarez-Gauthier A, López-Ríos F, Medina PP, Conde E, Tang M, Soler G, Lopez-Encuentra A, Cigudosa JC, Sanchez-Cespedes M. Expression signatures in lung cancer reveal a profile for EGFR-mutant tumours and identify selective PIK3CA overexpression by gene amplification. J Pathol 2008; 214: 347-356. Agulló-Ortuño MT, López-Ríos F, Paz-Ares L. Lung cancer genomic signatures. J Thorac Oncol 2010; 5: 1673-1691. Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F, Moch H, Olszewski W, Pauwels P, Penault-Llorca F, Rossi G. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch 2012; 461: 245-257. Conde E, Angulo B, Izquierdo E, Muñoz L, Suárez-Gauthier A, Plaza C, Dominguez N, Torres M, Madrigal L, Rubio-Viqueira B, Belda-Iniesta C, Hidalgo M, López-Ríos F. The ALK translocation in advanced non-small-cell lung carcinomas: preapproval testing experience at a single cancer centre. Histopathology 2013; 62: 609-616. Conde E, Suárez-Gauthier A, Benito A, Garrido P, García-Campelo R, Biscuola M, Paz-Ares L, Hardisson D, de Castro J, Camacho MC, Rodriguez-Abreu D, Abdulkader I, Ramirez J, Reguart N, Salido M, Pijuán L, Arriola E, Sanz J, Folgueras V, Villanueva N, Gómez-Román J, Hidalgo M, López-Ríos F. Accurate identification of ALK positive lung carcinoma patients: novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry. PLoS One 2014; 9: e107200. Bubendorf L, Büttner R, Al-Dayel F, Dietel M, Elmberger G, Kerr K, López-Ríos F, Marchetti A, Öz B, Pauwels P, Penault-Llorca F, Rossi G, Ryška A, Thunnissen E. Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch 2016; 469: 489-503. Kerr KM, López-Ríos F. Precision medicine in NSCLC and pathology: how does ALK fit in the pathway? Ann Oncol. 2016: Suppl 3:iii16-iii24. Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, Dietel M, Longshore JW, López-Ríos F, Penault-Llorca F, Viale G, Wotherspoon AC, Kerr KM, Tsao MS. Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non-Small-Cell Lung Cancer. J Clin Oncol 2017; 35: 3867-3876. Conde E, Caminoa A, Dominguez C, Calles A, Walter S, Angulo B, Sánchez E, Alonso M, Jimenez L, Madrigal L, Hernando F, Sanz-Ortega J, Jimenez B, Garrido P, Paz-Ares L, de Castro J, Hernandez S, Lopez-Rios F. Aligning digital CD8(+) scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma. Histopathology 2018; 72: 270-284. Yatabe Y, Dacic S, Borczuk AC, Warth A, Russell PA, Lantuejoul S, Beasley MB, Thunnissen E, Pelosi G, Rekhtman N, Bubendorf L, Mino-Kenudson M, Yoshida A, Geisinger KR, Noguchi M, Chirieac LR, Bolting J, Chung JH, Chou TY, Chen G, Poleri C, Lopez-Rios F, Papotti M, Sholl LM, Roden AC, Travis WD, Hirsch FR, Kerr KM, Tsao MS, Nicholson AG, Wistuba I, Moreira AL. Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer. J Thorac Oncol 2019; 14: 377-407. Büttner R, Longshore JW, López-Ríos F, Merkelbach-Bruse S, Normanno N, Rouleau E, Penault-Llorca F. Implementing TMB measurement in clinical practice: considerations on assay requirements. ESMO Open 2019; 4: e000442.

Dr Gerald Prager is an Associate Professor of Medicine, Board Certified for Internal Medicine Board and Certified for Haematology and Medical Oncology. In 2009, he received his M.D. from the University of Vienna. Currently, Dr Prager is Director of the Colorectal Cancer Unit of the Department of Medical Oncology at the Medical University of Vienna. He is also a member of the ESMO 2014 Scientific Committee. The research interest of his lab focuses on (tumour-) angiogenesis via regulation of endothelial cell survival and migration by cell / extracellular-matrix interaction. Through his clinical training in haemato-oncology, he became a member of the sought-after group of medical researches. He achieved his expertise in international renowned labs at University of California, San Diego, the Norris Cancer Center, Los Angeles and the Department of Vascular Biology, Mississippi University for Women (MUW). His work is honoured by 19 international awards and resulted in publications in international highly renowned journals. Dr Prager’s young research group is embedded in an international cancer research campus associated with Medical University of Vienna (MUV).