TRK fusion-positive cancer: new ESMO OncologyPRO learning resource

Ezra Cohen, MD, is co‐Director of the San Diego Center for Precision Immunotherapy and an internationally renowned translational researcher. A physician‐scientist, Dr Cohen led an independently funded laboratory interested in mechanisms of action of novel therapeutics. He has made major contributions to targeted and immunotherapy. His research has received peer‐reviewed funding in the study of epidermal growth factor receptor inhibitors, cell therapy, and immunotherapy in head and neck cancer. He has made major contributions to the understanding of critical signaling pathways, integration of novel agents into standard of care, and definition of mechanisms to overcome resistance to drug therapy. He has also recently co‐developed a personalized neoantigen vaccine using unique cancer mutations to boost an anti‐tumor immune response. Dr Cohen is Associate Director for Translational Science and leader of the Solid Tumor Therapeutics research program at Moores Cancer Center. He brings his expertise and preeminent reputation in head and neck cancer research and patient care to solid tumor therapeutics. Among other roles, he is chair of the Protocol Review and Monitoring Committee (PRMC) and serves as a member of the Cancer Council, and the Cancer Center’s Executive Committee. Dr Cohen recently served as editor‐in‐chief of Oral Oncology, the highest impact specialty journal in head and neck cancer, and currently serves as senior editor for Clinical Cancer Research. He has been the principal investigator on multiple studies of novel agents in head and neck cancer and other solid tumors in all phases of development including chemoprevention, phase I, II, and III trials. Dr Cohen has authored more than 170 papers and has presented his research at national and international meetings. In addition, he has served as a grant reviewer for the NIH, American Association for Cancer Research, American Society of Clinical Oncology, and the Ontario Institute for Cancer Research. Dr Cohen completed residencies in Family Medicine at the University of Toronto and in Internal Medicine at Albert Einstein College of Medicine. He completed a Hematology/Oncology fellowship at the University of Chicago where he was named chief fellow. Prior to his arrival in San Diego, Dr Cohen was Co‐Director of the Head and Neck Cancer Program, Associate Director for Education and Program Director for the Hematology/ Oncology Fellowship at the University of Chicago Comprehensive Cancer Center. A dedicated educator, Dr Cohen also mentored and developed young faculty in his program.

Frédérique PENAULT-LLORCA, MD, PhD, graduated as a medical specialist in pathology in 1993 and in oncology in 1995. Also, in 1995, she received a PhD from the Université d’Aix-Marseille II in cellular biology and microbiology, on the topic of HER2. Professor PENAULT-LLORCA is currently professor of Pathology at the University of Clermont-Ferrand, CEO of the Comprehensive Regional Cancer Institute Centre Jean PERRIN, deputy director of the research team INSERM 1240 IMoST, and head of the Molecular Biology Plateform at Centre Jean Perrin, Clermont-Ferrand, France, and Vice-President of UNICANCER GROUP. She chairs the Immuno- Oncology group at UNICANCER R&D. She is a member of several pathology and oncology societies (ESMO, ASCO, ECP, AIP, SFP. Her main areas of interest as a pathology being female cancers. Professor PENAULT-LLORCA has conducted various biomarkers-based research studies in breast, ovarian, colorectal, gastric, and lung cancer in relation to response to targeted therapies and immunotherapies. She also acts as a coordinating pathologist for various oncology trials. Professor PENAULT-LLORCA has written more than 440 peer-reviewed publications and several books on female cancers and biomarker testing methods and issues.

A medical oncologist, Silvia Stacchiotti works in the Adult Mesenchymal and Rare Tumor Medical Treatment Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milano, Italy. Dr Silvia Stacchiotti received his medical degree in 1993 in Milan, and trained at the INT. She is board certified in Medical Oncology. She has four children. She is involved in all institutional research activities on adult bone and soft tissue sarcomas (STS), including GIST. This includes neoadjuvant therapies in extremities and retroperitoneal STS, identification of new targets and new anticancer treatments for specific sarcoma types, studies on the immune-profile of sarcomas as well as on mechanisms of resistance to therapy and the development of preclinical models of sarcomas. She collaborates to the Italian Network on Rare Tumors. She is particularly dedicated to ultra-rare sarcomas, among which chordoma, chondrosarcoma, giant cell tumor of the bone, extraskeletal myxoid chondrosarcoma, alveolar soft part sarcoma, clear cell sarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, PEComa, vascular tumors, epithelioid sarcoma, desmoid tumor, tenosynovial giant cell tumor. She is the Principal Investigator of several Italian and International trials on sarcomas. She is the current president of the Italian Sarcoma Group (ISG). She is the faculty coordinator of the Sarcoma track of the European Society for Medical Oncology (ESMO) and the subject editor of the ESMO guidelines committee for sarcoma and GIST. She is a member of the Board of Directors of the Connective Tissue Oncology Society (CTOS). She is included in the list of European Medical Agency (EMA) external experts. She is the chair of the systemic therapy subcommittee of the EORTC Soft Tissue and Bone Sarcoma Group. She collaborates with several sarcoma Patients Advocacy Groups, among which the Chordoma Foundation, the Desmoid Tumor Research Foundation, the EHE Foundation, in which she serves as a member of the respective medical advisory boards. She has authored more than 200 scientific publications. She serves on the editorial board of European Journal of Cancer and Cancer

Andrea Sartore-Bianchi is the Director of the Division of Clinical Research and Innovation at Grande Ospedale Metropolitano Niguarda in Milano, Italy, and Associate Professor of Oncology at the University of Milano. He received his MD and postgraduate degree in Oncology at the University of Pavia, Italy, and subsequently conducted preclinical research at Brown University, Providence, RI, USA.

His main clinical and research interests include precision oncology and the treatment of gastrointestinal cancers, particularly colorectal carcinomas, focusing on biomarkers of sensitivity/resistance to targeted therapies. He is principal and co-investigator in Phase I-III clinical trials for solid tumours and carried out initial studies paving the way for the use of RAS and Her2 as tumor tissue/ctDNA biomarkers in colorectal cancer. He has published 200 peer-reviewed articles in various medical journals with a H-index of 62 (Scopus).

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. Rolfo MD, PhD, MBA, Dr, is the Director Ohio State Division of Medical Oncology and Associate director  of Clinical Research at the Center for Thoracic Oncology, Tisch Cancer Institute in Mount Sinai System . In addition, he is Professor of Medicine at the Division of Hematology and Oncology at Icahn School of Medicine, Mount Sinai, New York, NY, USA. From April 2018 to May 2021 he was serving as Director of Thoracic Medical Oncology and Director of Early Clinical Trials at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), in Baltimore, Maryland, USA. In addition, he was appointed Professor of Medicine at the Division of Oncology at Maryland University, School of Medicine. Prof. Rolfo is Medical Oncologist focused in Thoracic Oncology, Drug Development and Translational Oncology. From 2012 to March 2018 he was working as Director of the Phase I - Early Clinical Trials Unit, Director of the Clinical Trials Management Program at Antwerp University Hospital, and Senior Staff member of Thoracic Oncology Cluster at Antwerp University Hospital in Belgium. In addition he is Professor of Oncology at Antwerp University in the Center for Oncological Research (CORE) in Antwerp, Belgium, Professor Rolfo graduated with a degree in medicine from the National University of Córdoba, Argentina in 1996; he then studied at the University of Milan and the National Cancer Institute of Milan, Italy, receiving European Oncology Board certification in 2003, followed by Spanish Board Certification in Medical Oncology in 2007. He obtained a PhD and Doctor Europaeus in Clinical and Experimental Oncology Research cum laude from the University of Palermo, Italy in 2009 under the direction of Professor Rosell, and a Master of Business Health Administration from the Polytechnic University of Valencia, Spain in 2010. He worked as clinical researcher in the Spanish Lung Cancer Group in Mallorca, Spain for 8 years. He is actively working on drug development and Lung cancer & Mesothelioma treatment. His research is focused in molecular oncology and Immunotherapy in Thoracic Oncology and in a pan-tumoral approach, using new techniques in liquid biopsies, specifically in exosome isolation and circulating free tumour DNA. His group identify ALK translocation in exosomes in NSCLC patients, showed, for the first time, the videos of labeled EVs uptake by living lung cancer cells. He is currently working in the identification of new biomarkers involved in immunotherapy and TKI drug-resistance. In Drug development Prof. Rolfo contributed to the development of several compounds including Erlotinib, pharmacokinetics of Olaparib, Entrectinib among several drugs in early phase.