Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma

Frontiers in Oncology

Oncology

Krishna Goparaju¹  Priyanka S. Rana²  James J. Driscoll³ 

[1] Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, United States;Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States;Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, United States;Immune Oncology Program, Case Comprehensive Cancer Center, Cleveland, OH, United States;Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, United States;Immune Oncology Program, Case Comprehensive Cancer Center, Cleveland, OH, United States;Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States;

关键词: metabolism;    multiple myeloma;    proteasome inhibitor;    oxidative phosphorylation;    glycolysis;    fatty acid synthesis;   

DOI  :  10.3389/fonc.2023.1141851

 received in 2023-01-10, accepted in 2023-05-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway reprogramming in not only cancer cells but also surrounding cell types that contribute to anti-tumor immunity. Despite a vast amount of genetic and histologic heterogeneity within and between cancer types, a finite set of pathways are commonly deregulated to support anabolism, catabolism and redox balance. Multiple myeloma (MM) is the second most common hematologic malignancy in adults and remains incurable in the vast majority of patients. Genetic events and the hypoxic bone marrow milieu deregulate glycolysis, glutaminolysis and fatty acid synthesis in MM cells to promote their proliferation, survival, metastasis, drug resistance and evasion of immunosurveillance. Here, we discuss mechanisms that disrupt metabolic pathways in MM cells to support the development of therapeutic resistance and thwart the effects of anti-myeloma immunity. A better understanding of the events that reprogram metabolism in myeloma and immune cells may reveal unforeseen vulnerabilities and advance the rational design of drug cocktails that improve patient survival.

【 授权许可】

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Copyright © 2023 Rana, Goparaju and Driscoll