Preclinical and clinical research at the Cancer Center Amsterdam resulted in new therapeutic insights that supported FDA- and EMA- approval of these targeted biological therapies for lymphoma and leukemia patients. These success stories illustrate the interdependence and synergy of fundamental, translational and clinical research, and what the Cancer Center Amsterdam theme Target & Therapy Discovery is all about: from bench to bedside and back.
The work has been the result of a close collaboration of Cancer Center Amsterdam researchers Marcel Spaargaren and Steven Pals (Dept. of Pathology), Arnon Kater and Marie José Kersten (Dept. of Hematology), and Eric Eldering (Dept. of Exp. Immunology), of the Lymphoma and Myeloma Center Amsterdam (LYMMCARE).
Dr. M. Spaargaren
Dr. M. Spaargaren has a long-standing research interest in the molecular and cellular biology of B-cells and associated cancers. In collaboration with above-mentioned LYMMCARE researchers, his research team established that the unprecedented treatment effectiveness of Ibrutinib in (mature) B-cell malignancies, in particular chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström’s macroglobulinaemia (WM), is a consequence of a drug-induced restraining order against malignant cells to enter and stay within lymphoid organs. This exclusion deprives the cancerous cells of critical growth- and survival-signals.
Prof. Dr. E. Eldering
Prof. Dr. E. Eldering has a long-standing research interest in the regulation of cell death. In close collaboration with Prof. Dr. A. Kater, the (pre-)clinical efficacy of Venetoclax has been studied in CLL, including the tumor-mechanisms underlying drug-resistance, and the role of the lymphoid organs therein.
Prof. Dr. A. Kater
Prof. Dr. A. Kater is a hematologist and principal (inter)national investigator of several clinical studies on Venetoclax and Ibrutinib, either as single agent or combination therapy for CLL and MCL. He was the lead scientist on the practice-changing MURANO trial that led to the combination therapy of Venetoclax plus Rituximab as the new standard treatment for relapsed CLL.
Recently, Ibrutinib has received FDA- and EMA-approval for the treatment of CLL, MCL, WM and marginal zone lymphoma, and Venetoclax has been approved for the treatment of CLL and acute myeloid leukemia. Ibrutinib and Venetoclax, as well as other novel targeted biological therapies, are gradually replacing conventional chemo-immunotherapeutic treatment regimens and are expected to become the standard of care in the near future.
