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Targeting NTRK gene fusions on the ESMO OncologyPRO portal as a key resource relating to the detection and management of TRK fusion-positive cancer.


Targeting NTRK gene fusions

Prof. Andrea Sartore-Bianchi (medical oncologist), Assoc. Prof. Gerald Prager (medical oncologist), Dr Jaclyn Hechtman (molecular and surgical pathologist) and Prof. Fernando Lopez-Ríos (molecular and surgical pathologist) developed this educational resource.  With over 50,000 visits in 2 years, healthcare professionals continue to value the diagnostic and treatment guidance provided.

This resource aims to:

  1. Explore the importance of TRK fusion proteins as a therapeutic target and understand the clinical use of TRK inhibitors.
  2. Explain the mechanisms behind TRK fusion-driven tumour biology.
  3. Provide an overview of the different techniques used for NTRK gene fusion testing.
  4. Provide recommendations on testing for TRK fusion proteins

These topics are addressed over two modules. Module 1 provides an overview of cancers with NTRK gene fusions and their testing. Available treatments and those under development that target these fusions are also discussed. Module 2 provides an overview of how testing for NTRK gene fusions allows for the identification of patients who may benefit from TRK inhibitor therapy. The range of NTRK gene fusion testing methodologies available are reviewed.

COR2ED have donated this content to ESMO to ensure that the practical guide reflects today's best clinical practice in detecting and treating TRK fusion-positive 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.

Prof. Fernando López-Ríos has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

AstraZeneca, Bayer, BMS, Lilly, MSD, Pfizer, Roche, Takeda and Thermo Fisher. 

 

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.

Prof. Andrea Sartore-Bianchi has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Amgen, Bayer, Sanofi and Servier Pharmaceuticals. 

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).

Assoc. Prof. Gerald Prager has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Amgen, Arcus, Astellas, AstraZeneca, Bayer, BMS, CECOG, Incyte, Lilly, MSD, Merck Serono, Pierre Fabre, Roche, Servier, Takeda

 

 

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PRECISION ONCOLOGY CONNECT

PRECISION ONCOLOGY CONNECT is an initiative of COR2ED, supported by Independent Medical Educational Grants from AstraZeneca, Amoy Diagnostics and Bayer.

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