Dr Fieke Froeling - Molecular Subtypes and the Host in Pancreatic Cancer
Senior Clinical Lecturer in Pancreatic Cancer
Introduction
Pancreatic cancer continues to be almost universally lethal and is predicted to soon become the second highest cause of cancer death. To date, there has been little improvement in overall outcomes, with very few effective therapies available. We do, however, see exceptional tumour responses occasionally, where patients derive significant benefits and have better outcomes. Thus, there is an urgent need to personalise our patient care and better identify the right treatment for each patient.
Most of the observations in pancreatic cancer biology can be explained through basic evolutionary principles: it is a complex cancer that is adaptive, highly capable to thrive in a resource constrained environment and uniquely able to evade anti-cancer therapy. But how do cancer cells optimise their fitness, at the expense of the host, to progress into this deadly cancer? And, what can we learn from studying the alterations in the tumour and its microenvironment in the context of its host system? These are central questions driving my research, using well-annotated patient samples in conjunction with patient-derived preclinical model systems to identify novel therapeutic approaches and candidate biomarkers that can be tested in clinical trials.
Clinically, I am an Honorary Consultant Medical Oncologist at the Beatson West of Scotland Cancer Centre treating patients with pancreatic cancer. The overall goal is to develop personalised therapeutic strategies that emanate from discoveries in both basic science and reverse translation from clinical observation.
Biography
Education and qualifications
2020 ECFMG Certification, United States Medical Licensing Examination
2017 Postgraduate Diploma in Oncology, Institute of Cancer Research, London, UK
2017 Certificate of Completion of Training in Medical Oncology- General Medical Council, UK
2012 MRCP(UK) Royal College of Physicians UK
2011 PhD Barts Cancer Institute, Queen Mary University of London, UK
2006 M.D. Faculty of Medicine, University of Utrecht, The Netherlands
Appointments
2020-present: Clinical Senior Lecturer in Pancreatic Cancer, CRUK Scotland Institute and School of Cancer Sciences, University of Glasgow, UK
Oncology Lead, Glasgow Precision Oncology Laboratory (GPOL),Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, UK
Honorary Consultant Medical Oncologist, Beatson West of Scotland Cancer Centre, NHS Greater Glasgow and Clyde, Glasgow, UK
2020–2020 Consultant Medical Oncologist, Edinburgh Cancer Centre, Edinburgh, UK
2017–2020 Donaldson Translational Research Fellow, Cold Spring Harbor Laboratory, NY, USA
2017–2020 Instructor in Medical Oncology, Northwell Health, NY, USA
2019–2020 Clinical Observer Fellowship, Memorial Sloan-Kettering Cancer Center, NY, USA
2017–2020 Honorary Clinical Senior Lecturer, Imperial College London, UK
2013–2017 NIHR Academic Clinical Lecturer, Imperial College London, UK
2013–2013 Specialist Registrar Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK
2011–2013 Core Medical Training, Ipswich Hospital NHS Trust, Ipswich, UK
2009–2010 Honorary Clinical Fellow Acute Medicine, Barts and The London NHS Trust, London, UK
2007–2011 Clinical Research Fellow, Centre for Tumour Biology, Barts Cancer Institute, London, UK
Current committee membership
Member of the Independent Data Monitoring Committee for STARPAC2 (PRIMUS-005); UK
Member of the Global Alliance for Genomics and Health (GA4GH) Equity, Diversity, and Inclusion (EDI) Advisory Group; International
Member of Lustgarten Foundation Translational Advisory Group; USA
Co-chair of Trial Management Group for PRIMUS-004; UK
Member of Trial Management Group for PASS-01; USA and Canada
Co-chair of Polyethnic-1000 Steering Committee; USA
Affiliate member of New York Genome Center Cancer Group; USA
Member of ICGC – ARGO Tissue and Clinical Annotation Working Group; International
Recent Publications
2024
Pea A, He X, Upstill-Goddard R, Luchini C, Santana LPS, Dreyer S, Duthie F, Jamieson NB, McKay CJ, Dickson EJ, Pulvirenti A, Rebus S, Piccoli P, Sperandio N, Lawlor RT, Milella M, Froeling FEM, Salvia R, Scarpa A, Bainkin AV, Wedge DC, Chang DK. Clonal evolutionary analysis reveals patterns of malignant transformation in pancreatic cancer from Intraductal Papillary Mucinous IPMN Neoplasms (IPMN). bioRxiv. 2024:2024.2008.2002.606217.
2023
Bergamini A, Ramaswami R, Froeling F, Papanastasopoulos P, Short D, Aguiar X, Savage PM, Sarwar N, Kaur B, Saso S, Fotopoulou C, Sharma A, Rustin GJS, Seckl M. Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study. Int J Gynecol Cancer. 2023;33(11):1750-1756.
Chung T, Garcia L, Swamynathan MM, Froeling FEM, Trotman LC, Tuveson DA, Lyons SK.Internally Controlled and Dynamic Optical Measures of Functional Tumor Biology. Anal Chem. 2023; 95: 5661–5670
2022
Bryce AS, Dreyer SB, Froeling FEM, Chang DK. Exploring the Biology of Cancer-Associated Fibroblasts in Pancreatic Cancer. Cancers (Basel). 2022;14:5302
2021
Casolino R, Paiella S, Azzolina D, Beer PA, Corbo V, Lorenzoni G, Gregori D, Golan T, Braconi C, Froeling FEM, Milella M, Scarpa A, Pea A, Malleo G, Salvia R, Bassi C, Chang DK, Biankin AV. Homologous Recombination Deficiency in Pancreatic Cancer: A Systematic Review and Prevalence Meta-Analysis. J Clin Oncol. 2021;39: 2617-2631
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, Paris C, Lampraki EM, Dray E, Serrels B, Caligiuri G, Rebus S, Plenker D, Galluzzo Z, Brunton H, Cunningham R, Tesson M, Nourse C, Bailey UM, Jones M, Moran-Jones K, Wright DW, Duthie F, Oien K, Evers L, McKay CJ, McGregor GA, Gulati A, Brough R, Bajrami I, Pettitt S, Dziubinski ML, Candido J, Balkwill F, Barry ST, Grützmann R, Rahib L; Glasgow Precision Oncology Laboratory,; Australian Pancreatic Cancer Genome Initiative, Johns A, Pajic M, Froeling FEM, Beer P, Musgrove EA, Petersen GM, Ashworth A, Frame MC, Crawford HC, Simeone DM, Lord C, Mukhopadhyay D, Pilarsky C, Tuveson DA, Cooke SL, Jamieson NB, Morton JP, Sansom OJ, Bailey PJ, Biankin AV, Chang DK. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2021;160(1):362-377.
Casolino R, Braconi C, Malleo G, Paiella S, Bassi C, Milella M, DreyerSB, Froeling FEM, Chang DK, Biankin AV, Golan T. Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine. Annals of Oncology. 2021;32:183-196.
Froeling FEM, Casolino R, Pea A, Biankin AV, Chang DK. Molecular Subtyping and Precision Medicine for Pancreatic Cancer. J Clin Med. 2021;10: 149
2020
Brunton H, Caligiuri G, Cunningham R, Upstill-Goddard R, Bailey UM, Garner IM, Nourse C, Dreyer SB, Jones M, Moran-Jones K, Wright DW, Paulus-Hock V, Nixon C, Thomson G, Jamieson NB, McGregor GA, Evers L, McKay CJ, Gulati A, Brough R, Bajrami I, Pettit S, Dziubinski ML, Barry ST, Grützmann R, Brown R, Curry E, Glasgow Precision Oncology Laboratory, Australian Pancreatic Cancer Genome Initiative, Pajic M, Musgrove EA, Petersen G, Shanks E, Ashworth A, Crawford HC, Simeone DM, Froeling FEM, Lord CJ, Mukhopadhyay D, Pilarsky C, Grimmond SE, Morton JP, Sansom OJ, Chang DK, Bailey P, Biankin AV. HNF4A and GATA6 loss reveals therapeutically actionable subtypes in pancreatic cancer. Cell Reports. 2020;31(6):107625.
Chan-Seng-Yue M, Kim JC, Wilson GW, Ng K, Flores Figueroa F, O’Kane GM, Connor AA, Denroche RE, Grant RC, McLeod J, Wilson JM, Ho Jang G, Zhang A, Liang SB, Borgida A, Chadwick D, Kalimuthu S, Lungu I, Bartlett JMS, Krzyzanowski PM, Sandhu V, Tiriac H, Froeling FEM, Karasinska JM, Topham JT, Renouf DJ, Schaeffer DF, Jones SJM, Marra MA, Laskin J, Chetty R, Stein LD, Zogopoulos G, Haibe-Kains B, Campbell PJ, Tuveson DA, Knox JJ, Fischer SE, Gallinger S, Notta F. Transcription phenotypes of pancreatic cancer are driven by genomic events during tumour evolution. Nat Genet. 2020;52(2):231-240.
Kocher HM, Basu B, Froeling FEM, Sarker D, Slater S, Carlin D, deSouza NM, De Paepe KN, Goulart MR, Hughes C, Imrali A, Roberts R, Pawula M, Houghton R, Lawrence C, Yogeswaran Y, Mousa K, Coetzee C, Sasieni P, Prendergast A, Propper DJ. Phase I clinical trial repurposing all-trans retinoic acid (ATRA) as a stromal targeting 1 agent for pancreatic cancer (STARPAC). Nat Commun. 2020;11(1):4841.
2019
Froeling FEM, Swamynathan MM, Deschênes A, Chio IIC, Brosnan E, Yao MA, Alagesan P, Lucito M, Li J, Chang AY, Trotman LC, Belleau P, Park Y, Rogoff HA, Watson JD, Tuveson DA. Bioactivation of napabucasin triggers reactive oxygen species–mediated cancer cell death. Clin Cancer Res. 2019;25(23):7162-7174.
Froeling FEM, Ramaswami R, Papanastasopoulos P, Kaur B, Sebire NJ, Short D, Fisher RA, Sarwar N, Wells M, Singh K, Ellis L, Horsman JM, Winter MC, Tidy J, Hancock BW, Seckl MJ. Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours. Br J Cancer. 2019;120(6):587-594.
2018
Tiriac H, Belleau P, Engle DD, Plenker D, Deschênes A, Somerville TDD, Froeling FEM, Burkhart RA, Denroche RE, Jang GH, Miyabayashi K, Young CM, Patel H, Ma M, LaComb JF, Palmaira RLD, Javed AA, Huynh JC, Johnson M, Arora K, Robine N, Shah M, Sanghvi R, Goetz AB, Lowder CY, Martello L, Driehuis E, LeComte N, Askan G, Iacobuzio-Donahue CA, Clevers H, Wood LD, Hruban RH, Thompson E, Aguirre AJ, Wolpin BM, Sasson A, Kim J, Wu M, Bucobo JC, Allen P, Sejpal DV, Nealon W, Sullivan JD, Winter JM, Gimotty PA, Grem JL, DiMaio DJ, Buscaglia JM, Grandgenett PM, Brody JR, Hollingsworth MA, O'Kane GM, Notta F, Kim E, Crawford JM, Devoe C, Ocean A, Wolfgang CL, Yu KH, Li E, Vakoc CR, Hubert B, Fischer SE, Wilson JM, Moffitt R, Knox J, Krasnitz A, Gallinger S, Tuveson DA. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov. 2018;8(9):1112-1129.
Ul-Haq I, Dalla Pria A, Suardi E, Pinato DJ, Froeling FEM, Forni J, Randell P, Bower M. Blood Epstein-Barr virus DNA does not predict outcome in advanced HIV-associated Hodgkin lymphoma. Med Oncol. 2018;35(4):53.
Froeling FEM, Tuveson DA. Pancreatic cancer foiled by a switch of tumour subtype. Nature. 2018;557(7706):500-501.