University of Navarra
Pamplona, Navarra, Spain
Department: Hemato-Oncology
Multiple myeloma (MM) is an incurable neoplasm, preceded by a benign phase of the disease (MGUS and SMM). The transformation from MGUS-SMM to MM has been well characterized at genetic level, but so far the modifications that do not alter the genetic code but give rise to changes in gene expression (Epigenome) have not been studied. In this proposal, we will characterize the Epigenome of this transformation from MGUS-SMM to MM in order to identify potential aberrations that allow us to develop new therapeutic strategies for the treatment of patients with this disease.
La Jolla, CA, USA
This proposal, entitled, “Tuning the innate immune multiple myeloma microenvironment by modulating IRF4,” will endeavor to reprogram myeloma-associated macrophages while simultaneously eradicating malignant plasma cells through selective inhibition of IRF4 in preclinical multiple myeloma models. This research will contribute vital knowledge about the potential impact of anti-inflammatory macrophages on myeloma cell survival and their relevance to the treatment of cancer. We anticipate that the results of our proposed Aims will be rapidly translated into improving treatments for patients with multiple myeloma because we will be exploring the mechanism of action of a state-of-the-art antisense therapeutic agent recently entered clinical trials for MM (NCT04398485). This project is potentially transformative for the diagnosis and treatment of multiple myeloma because it has the potential to distinguish IRF4 antisense therapy as a two-pronged molecular targeting approach that could eradicate tumor cells along with reprogramming the tumor-supportive microenvironment.
Funded by: Angela (Dirks) Barto Memorial Golf Tournament – Chad Barto
Parma, Italy
Multiple myeloma (MM) cancer cells are craving for the amino acid glutamine that is rapidly taken up depleting bone marrow. Thus, other cell populations in the bone marrow undergo glutamine shortage and are forced to synthesize the amino acid for the malignant cells. As a consequence, bone marrow stromal cells acquire a pro-tumor behavior. Therefore, drugs that limit glutamine consumption of cancer cells or glutamine production and secretion by stromal
cells are expected to hinder MM progression.
Czerkies Memorial Golf Outing – Craig Czerkies
Catania, Italy
Myeloma cells can survive in arginine starvation, which is toxic for T-cells, to hamper immune function, leading to infections, treatment refractoriness and disease progression.
Our strong preliminary data revealed a new molecular mechanism, used preferentially in secreting cells, for quick recycling of nucleotides and aminoacids during arginine starvation, called UFMylation, never described before in myeloma. We aim to better understand how UFMylation works in myeloma, and if it is possible to target it to increase the effectiveness of bortezomib (a drug widely used for myeloma treatment) and to identify the underlying mechanisms through which inhibition takes place.
Funded by: Miles for Myeloma 5K Run/Walk – IMF