Molecular and translational oncology of pancreatic and esophageal cancers
Our group aims to understand the tumor biology that explains the poor outcome of upper GI cancers, and ultimately improve the treatment of these diseases. Projects running in the group fall under three major themes:
Maarten Bijlsma
How does cellular plasticity contribute to therapy resistance?
Tumor cells from the upper GI tract are hallmarked by a remarkable flexibility: Depending on their environment or exposure to for instance (chemo)therapy, these cells can change important biological features and by doing so escape effective treatment. Our research aims to unravel why in particular these upper GI cancer cells harbor such plasticity, how this plasticity contributes to tumorigenesis and therapy resistance, and how we can measure and target its occurrence in patients.
How do cancers grow?
Which of the cells in a tumor tissue contribute to its growth is not known. Likewise, it is not known which population of cells has the true potential to metastasize, and whether that ability is cell-intrinsically defined. Within the group’s research, animal models for tumor growth are used in conjunction with genetic labeling methods to delineate when and where tumor cells contribute to growth. These insights are especially pertinent in cancers such as pancreatic adenocarcinoma, where early dissemination is known to drive poor outcome.
Which differences exist between tumors and what is the relevance of this for treatment?
At all levels of biological information (from DNA up to active proteins), tumors differ from each other. This heterogeneity is known to impact on the efficacy of treatment in unselected patient cohorts. In the research program, the heterogeneity between and within tumors is charted at the levels of gene expression, metabolism, and phosphoproteins. The consequences for current treatments are determined, and the possibilities for novel treatments are considered.
These themes interconnect and recur in the lab’s research projects. For instance, the contributions of the collective of non-tumor cells known as the stroma is an important element across themes. In addition, a biomarker discovery effort is associated with most projects, and the program is closely affiliated with several important biobanking infrastructures to allow this. Likewise, clinical stakeholders are involved to increase likelihood of translation. Based on findings and biomarkers from the research program, clinical trials have indeed been designed and initiated.
Group members
Deni van Schie
Dionne Blangé1
Ines Avenel1
Job Kesselaar2
Marjolein Lansbergen1
Paul Manoukian1
Rebecca Roessler3
Romy Ros
Tim van der Plas2
Benthe Doeve1
Linde Veen1
1 co-supervised with Hanneke van Laarhoven
2 co-supervised with Louis Vermeulen
3 co-supervised with Jan Paul Medema
Key publications
Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases
Bootsma S, Dings MPG, Kesselaar J, Helderman RFCPA, van Megesen K, Constantinides A, Moreno LF, Stelloo E, Scutigliani EM, Bokan B, Torang A, van Hooff SR, Zwijnenburg DA, Wouters VM, van de Vlasakker VCJ, Galanos LJK, Nijman LE, Logiantara A, Veenstra VL, Schlingemann S, van Piggelen S, van der Wel N, Krawczyk PM, Platteeuw JJ, Tuynman JB, de Hingh IH, Klomp JPG, Oubrie A, Snaebjornsson P, Medema JP, Oei AL, Kranenburg O, Elbers CC, Lenos KJ, Vermeulen L, Bijlsma MF.
Cell Rep Med. 2024 May 21;5(5):101523.
Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer
Dings MPG, van der Zalm AP, Bootsma S, van Maanen TFJ, Waasdorp C, van den Ende T, Liu D, Bailey P, Koster J, Zwijnenburg DA, Spek CA, Klomp JPG, Oubrie A, Hooijer GKJ, Meijer SL, van Berge Henegouwen MI, Hulshof MC, Bergman J, Oyarce C, Medema JP, van Laarhoven HWM, Bijlsma MF.
Cell Rep Med. 2022 Nov 15;3(11):100802.
Continuous clonal labeling reveals uniform progenitor potential in the adult exocrine pancreas
Lodestijn SC, van den Bosch T, Nijman LE, Moreno LF, Schlingemann S, Sheraton VM, van Neerven SM, Koning JJ, Vieira Braga FA, Paauw NJ, Lecca MC, Lenos KJ, Morrissey E, Miedema DM, Winton DJ, Bijlsma MF*, Vermeulen L*.
Cell Stem Cell. 2021 Nov 4;28(11):2009-2019.e4
Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma
Ebbing EA, van der Zalm AP, Steins A, Creemers A, Hermsen S, Rentenaar R, Klein M, Waasdorp C, Hooijer GKJ, Meijer SL, Krishnadath KK, Punt CJA, van Berge Henegouwen MI, Gisbertz SS, van Delden OM, Hulshof MCCM, Medema JP, van Laarhoven HWM, Bijlsma MF.
Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2237-2242.
Molecular subtypes in cancers of the gastrointestinal tract
Bijlsma MF, Sadanandam A, Tan P, Vermeulen L.
Nat Rev Gastroenterol Hepatol. 2017 Jun;14(6):333-342.
Contact information
m.f.bijlsma@amsterdamumc.nl
020-56 67777
Keywords
pancreatic cancer | esophageal cancer | stroma | drug discovery | biomarkers | tumor biology