Research team Simon Ekman

Translational and clinical research in thoracic oncology.

Molecular characterization of non-small cell lung cancer.
Molecular characterization of non-small cell lung cancer.

Research

Our research focuses on thoracic oncology, mainly lung cancer, and includes both clinical, translational and preclinical studies. We aim to find new treatment targets and biomarkers that are important for prognosis and treatment response, especially in the areas of lung cancer. For this purpose, we have established patient cohorts where we have collected detailed clinical data and associated tumor material for molecular analyses. Resistance to therapy is a common clinical issue in the treatment of lung cancer and is an important reason for poor prognosis. A major focus of our translational and clinical lung cancer research is the identification of mechanisms of resistance to and biomarkers for tyrosine kinase inhibitors, mainly of EGFR and ALK, and immunotherapy. An important aim is to improve diagnostics and treatment using precision cancer medicine. This involves research programs in diagnostics, imaging, treatments and cancer registers as well as preclinical and translational projects. In these projects we are involving patients treated in clinical routine at Karolinska University Hospital as well as in different clinical studies.

Another focus of research is the important clinical issue of brain metastasis in lung cancer, which is a patient group with a poor prognosis. This involves investigation of molecular mechanisms of brain metastasis in lung cancer and development of novel therapeutics. These studies involve analyses of brain metastasis tissue and cerebrospinal fluid (CSF) with a focus on treatment with targeted therapies. We perform exosome analysis in the collected specimens, where exosomes have been shown to be released from tumor cells and to carry DNA and RNA reflecting the molecular profiles of the solid tumor tissues. In another brain metastasis study in lung cancer, we have performed an imaging study of uptake of an EGFR tyrosine kinase inhibitor in the brain using PET imaging and radiolabeled drug with the aim to identify and understand response and resistance in treatment of brain metastasis.

Selected collaborations: Swedish Lung Cancer Study Group, National Lung Cancer Register, Oslo University (PIs Prof Odd Terje Brustugun, Prof Åslaug Helland), University of Copenhagen/Rigshospitalet (PI Prof Jens Benn SØrensen), Uppsala University (PIs Prof Johan Botling, Prof Patrick Micke, Dr Georg Holgersson), Umeå University (PI Prof Michael Bergqvist), University of Manchester/Christie Hospital (PI Dr Raffaele Califano), University of Colorado Denver (PI Prof Fred Hirsch), University of Crete/University General Hospital Heraklion (PI Prof Dimitris Mavroudis).

Team members 

Gunnar Wagenius, MD, PhD, Associate Professor
Per Hydbring, PhD, PI, collaborator  
Konstantinos Rounis, MD
Georgios Tsakonas, MD, PhD, Postdoc
Zeinab Kosibaty, PhD, Postdoc, collaborator
Caroline Kamali, MD, PhD-student
Marcus Skribek, MD, PhD-student
Hirsh Koyi, affiliated
Signe Friesland, affiliated

Selected publications (2016-2021)

High density of NRF2 expression in malignant cells is associated with increased risk for CNS metastasis in early stage NSCLC
Tsakonas G, Martín-Bernabé A, Rounis K, Moreno-Ruiz P, Botling J, De Petris L, Ylipää A, Mezheyeuski A, Micke P, Östman A, Ekman S.
Accepted for publication in Cancers, June 2021.

Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy.
Rounis K, Skribek M, Makrakis D, De Petris L, Agelaki S, Ekman S, Tsakonas G
Cancers (Basel) 2021 Mar;13(7):

An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer.
Tsakonas G, Lewensohn R, Botling J, Ortiz-Villalon C, Micke P, Friesland S, Nord H, Lindskog M, Sandelin M, Hydbring P, Ekman S
Eur J Cancer 2020 06;132():24-34

ALK-Brain Prognostic Index-Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases.
Tsakonas G, Kamali C, De Petris L, Friesland S, Lewensohn R, Ekman S
Cancers (Basel) 2020 Jul;12(7):

Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a 'Real-Life' Setting.
Skribek M, Rounis K, Makrakis D, Agelaki S, Mavroudis D, De Petris L, Ekman S, Tsakonas G
Cancers (Basel) 2020 Dec;12(12):

Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study).
Eide IJZ, Helland Å, Ekman S, Mellemgaard A, Hansen KH, Cicenas S, Koivunen J, Grønberg BH, Brustugun OT
Lung Cancer 2020 05;143():27-35

c-MET as a biomarker in patients with surgically resected non-small cell lung cancer.
Tsakonas G, Botling J, Micke P, Rivard C, LaFleur L, Mattsson J, Boyle T, Hirsch FR, Ekman S
Lung Cancer 2019 07;133():69-74

miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC.
Lai Y, Kacal M, Kanony M, Stukan I, Jatta K, Kis L, Norberg E, Vakifahmetoglu-Norberg H, Lewensohn R, Hydbring P, Ekman S
Biochem Biophys Res Commun 2019 04;511(2):260-265

Exosomal RNA-profiling of pleural effusions identifies adenocarcinoma patients through elevated miR-200 and LCN2 expression.
Hydbring P, De Petris L, Zhang Y, Brandén E, Koyi H, Novak M, Kanter L, Hååg P, Hurley J, Tadigotla V, Zhu B, Skog J, Viktorsson K, Ekman S, Lewensohn R
Lung Cancer 2018 10;124():45-52

A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial.
Ekman S, Harmenberg J, Frödin JE, Bergström S, Wassberg C, Eksborg S, Larsson O, Axelson M, Jerling M, Abrahmsen L, Hedlund Å, Alvfors C, Ståhl B, Bergqvist M
Acta Oncol 2016 ;55(2):140-8

Funding bodies

CF-Cancerfonden, KIS/KIF, EP-Erling Persson, Sjöbergstiftelsen, VR- Vetenskapsrådet, SLS-Svenska Läkaresällskapet, Cancer Research KI, Oasmia, FoUU, Takeda, Radiumhemmets Forskningsfonder.