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Project
Drug resistance in multiple myeloma: study of extrinsic mechanisms governed by the bone marrow microenvironment (FWOAL728)
Multiple myeloma (MM) is a hematological cancer affecting approximately 25000
new patients in the EU. The introduction of new therapies including novel agents such
as proteasome inhibitors and immunomodulatory drugs has led to a significantly
improved survival rate. However, relapse of the disease, as the result of the
emergence of drug-resistant MM cells remains the main obstacle on the road to a
cure. Resistance can either be explained by the presence of a drug resistant population
or by the acquisition of additional genetic lesions during its progression to more
aggressive states or by the protection of the microenvironment against different
therapies. The bone marrow (BM) microenvironment is indeed crucial for MM
progression and includes a mix of cell types such as stromal cells, bone cells, immune
cells, and myeloid cells. This project aims to study the latter extrinsic mechanisms of
resistance to known drugs.
We will investigate how BM stromal cells (and focus more specifically on tumor
associated fibroblasts and macrophages) influence the drug response of the MM cells
(also in an hypoxic environment). In the last work package we will also assess the
epigenetic regulation mediated by the microenvironment. The different work
packages interact with each other and are complementary with the studies on intrinsic
mechanisms of tumor resistance, also studied in our laboratory and may offer clues to
new targets to overcome drug resistance.
new patients in the EU. The introduction of new therapies including novel agents such
as proteasome inhibitors and immunomodulatory drugs has led to a significantly
improved survival rate. However, relapse of the disease, as the result of the
emergence of drug-resistant MM cells remains the main obstacle on the road to a
cure. Resistance can either be explained by the presence of a drug resistant population
or by the acquisition of additional genetic lesions during its progression to more
aggressive states or by the protection of the microenvironment against different
therapies. The bone marrow (BM) microenvironment is indeed crucial for MM
progression and includes a mix of cell types such as stromal cells, bone cells, immune
cells, and myeloid cells. This project aims to study the latter extrinsic mechanisms of
resistance to known drugs.
We will investigate how BM stromal cells (and focus more specifically on tumor
associated fibroblasts and macrophages) influence the drug response of the MM cells
(also in an hypoxic environment). In the last work package we will also assess the
epigenetic regulation mediated by the microenvironment. The different work
packages interact with each other and are complementary with the studies on intrinsic
mechanisms of tumor resistance, also studied in our laboratory and may offer clues to
new targets to overcome drug resistance.
Date:1 Jan 2014 → 31 Dec 2017
Keywords:Blood, Stem Cell, Coagulation, Myeloma, Immunology, Microbiology, HLA, Hematology, Lymphoma, cancer, Bone Marrow Transplantation
Disciplines:Hematology, Immunology, Oncology, Microbiology