Mutant KRAS Enhances Stress Granules and Resistance to Proteasome Inhibition Via 15-d-PGJ2 in Multiple Myeloma

Mutant KRAS Enhances Tumor Cell Fitness by Upregulating Stress Granules

There is growing evidence that stress-coping mechanisms represent tumor cell vulnerabilities that may function as therapeutically beneficial targets. Recent work has delineated an integrated stress adaptation mechanism that is characterized by the formation of cytoplasmic mRNA and protein foci, termed stress granules (SGs). Here, we demonstrate that SGs are markedly elevated in mutant KRAS cell...

Resistance to Proteasome Inhibitors in Multiple Myeloma

Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells in the bone marrow associated with a spectrum of clinical symptoms including bone destruction, anemia, hypercalcemia, and renal failure. Although MM remains incurable, a dramatic paradigm shift in the treatment of MM has occurred over the past decade through the introduction of novel agents, including the development of s...

Proteasome Inhibition and Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Proteasome inhibition and its therapeutic potential in multiple myeloma

Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years. In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease. In this article, we briefly r...

osteogenic inhibition in multiple myeloma

objective: multiple myeloma (mm) is a plasma cell malignancy where plasma cells are increased in the bone marrow (bm) and usually do not enter peripheral blood, but produce harmful factors creating problems in these patients (e.g. malignant plasma cells over activate osteoclasts and inhibit osteoblasts with factors like rankl and dkk). these factors are a main cause of bone lesion in mm patient...