My research focus is finding better therapies for patients with gastroesophageal cancer (GEA) by studying the biological foundation of the disease. As a physician scientist I use a bedsite-to bench approach and search solutions for clinical problems in the lab. In recent years it has become increasingly apparent that GEA occurs in distinct genomic subtypes with distinct immune infiltrates which influence response to antineoplastic therapies. My group studies how GEA cells shape their immune microenvironment and how a pre-existing immune infiltrate influences response to standard care and how to overcome therapy resistance.

Sarah Derks

Photo taken by Marlou Pulles

To better understand the microenvironment of GEAs we characterize patient-derived tumor samples using advanced molecular approaches, such as spatial transcriptomics and secretome analyses. Thereby we found important leads to how we should target the immune microenvironment to improve outcome to chemoradiotherapy. Further, we leveraged fresh patient tissue to generate a biobank of tumor organoids with matched tumor-infiltrating lymphocytes and established co-culture models. These in vitro systems allow us to screen for novel and alternative therapeutic opportunities for GEAs. Additionally, we established an immunogenic GEA mouse model which we use to evaluate the role of known immunomodulatory pathways in mediating resistance to immune checkpoint inhibitors. Lastly, we aim to translate our findings to early-stage clinical trials with the ultimate goal to identify novel targeted immunomodulatory strategies and improve survival of patients with this deadly disease.

We highly value our collaborations and enjoy working closely with Prof. Tanja de Gruijl (Medical Oncology, Amsterdam UMC) and her Immunotherapy Lab, Prof. Hanneke van Laarhoven (Medical Oncology, Amsterdam UMC), Prof. Maarten Bijlsma, Dr. Joep Grootjans (Gastroenterology, Amsterdam UMC; Oncode Researcher), Dr. Jan Van den Bossche (Molecular Cell Biology and Immunology, Amsterdam UMC), and Dr. Victor Thijssen (Radiation Oncology, Amsterdam UMC).

Group members

Group Members

  • Sarah Derks
  • Maryam Akbarzadeh
  • Jens Seidel
  • Daniëlle Polling
  • Jasper Sanders
  • Rosalia Franco Fernandez
  • Kayla Brugman
  • Rok Žiberna
  • Sterre Kruize
  • Julia Myrda

                      Key publications

                      Groen-van Schooten TS, Franco Fernandez R, van Grieken NCT, et al. Mapping the complexity and diversity of tertiary lymphoid structures in primary and peritoneal metastatic gastric cancer. J Immunother Cancer. 2024;12(7):e009243. doi:10.1136/jitc-2024-009243

                      Groen-van Schooten TS, Harrasser M, Seidel J, et al. Phenotypic immune characterization of gastric and esophageal adenocarcinomas reveals profound immune suppression in esophageal tumor locations. Front Immunol. 2024;15:1372272. doi:10.3389/fimmu.2024.1372272

                      van den Bosch T, Derks S, Miedema DM. Chromosomal Instability, Selection and Competition: Factors That Shape the Level of Karyotype Intra-Tumor Heterogeneity. Cancers (Basel). 2022;14(20):4986. doi:10.3390/cancers14204986

                      de Klerk LK, Patel AK, Derks S, et al. Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. J Immunother Cancer. 2021;9(9):e002472. doi:10.1136/jitc-2021-002472

                      de Klerk LK, Goedegebuure RSA, van Grieken NCT, et al. Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies. Mol Oncol. 2021;15(4):901-914. doi:10.1002/1878-0261.12907

                      Goedegebuure RSA, Harrasser M, de Klerk LK, et al. Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma. Oncoimmunology. 2021;10(1):1954807. doi:10.1080/2162402X.2021.1954807

                      Derks S, de Klerk LK, Xu X, et al. Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas. Ann Oncol. 2020;31(8):1011-1020. doi:10.1016/j.annonc.2020.04.011

                      Pectasides E, Stachler MD, Derks S, et al. Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma. Cancer Discov. 2018;8(1):37-48. doi:10.1158/2159-8290.CD-17-0395

                      Cancer Genome Atlas Research Network, Analysis Working Group: Asan University, BC Cancer Agency, et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541(7636):169-175. doi:10.1038/nature20805

                      Derks S, Nason KS, Liao X, et al. Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma. Cancer Immunol Res. 2015;3(10):1123-1129. doi:10.1158/2326-6066.CIR-15-0046

                      Contact information

                      E: s.derks@amsterdamumc.nl
                      T: +31 20 4443210
                      Website Oncode: www.oncode.nl/research/groups/sarah-derks-group

                        Keywords

                        Gastroesophageal Cancer | Translational Research | Immunology | Tumor Microenvironment | Clinical Studies.