Dr. Marcel Spaargaren is leader of the theme ‘Target discovery & pre-clinical therapy development’ within the program Tumor Biology and Immunology of the Cancer Center Amsterdam. He is associate professor at the department of Pathology at the Academic Medical Center and board-member of the Lymphoma and Myeloma Center Amsterdam (LYMMCARE). Furthermore, he is chair of the society for Tumor Cell Biology of the Dutch Cancer Society (KWF) and dean of the Oncology Graduate School Amsterdam (OOA).
Major aims of his research are:
- Identify and molecularly dissect the signaling pathways involved in the pathogenesis of B-cell malignancies.
- Explore and exploit microenvironment-dependence as the Achilles’ heel of B-cell malignancies.
More specifically, focussing on multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), his research group has studied the molecular and functional aspects of signalling by the B-cell antigen receptor, chemokines, HGF/MET, and WNTs, and the role of the GTPase Ral, heparan sulfate proteoglycans, adhesion molecules (integrins and cadherins), Bruton’s tyrosine kinase, and the transcription factor FOXP1.
One of his major and long-standing research lines involves the molecular and functional aspects of B-cell receptor-controlled integrin-mediated adhesion and chemokine-controlled adhesion and migration of normal and malignant B cells. His previous studies have established a critical role for Bruton’s tyrosine kinase (BTK) in these processes and his recent studies on the molecular mechanism underlying the unprecedented clinical efficacy of the recently FDA-approved Bruton’s tyrosine kinase (BTK) inhibitor Ibrutinib and the phospatidylinositol-3 kinase δ (PI3K δ) inhibitor Idelalisib in B-cell malignancies, in particular CLL and MCL, have established integrin-mediated lymphoid organ retention, homing and microenvironment-dependence as a prominent therapeutic target for treatment of B-cell malignancies.