Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?

Frontiers in Oncology

Kylee Lyons¹  Christopher Lamb¹  Alisher Baibussinov¹  Alexandra Yamada¹  Martin Sarafyan¹  Nicole Jacobs¹  Mysore Veena²  Gilberto Gastelum²  Patrick Frost²  Jeffry Kraut²  Rebeka Shamis² 

[1] Department of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA, United States;Department of Research, Greater Los Angeles Veterans Administration Healthcare System, Los Angeles, CA, United States;

关键词: pH balance;    acid base regulation;    bone marrow microenvironment;    hypoxia and apoptosis;    multiple myeloma;   

DOI  :  10.3389/fonc.2021.703878

来源: DOAJ

【 摘 要 】

Multiple myeloma (MM) is an incurable cancer arising from malignant plasma cells that engraft in the bone marrow (BM). The physiology of these cancer cells within the BM microenvironment (TME) plays a critical role in MM development. These processes may be similar to what has been observed in the TME of other (non-hematological) solid tumors. It has been long reported that within the BM, vascular endothelial growth factor (VEGF), increased angiogenesis and microvessel density, and activation of hypoxia-induced transcription factors (HIF) are correlated with MM progression but despite a great deal of effort and some modest preclinical success the overall clinical efficacy of using anti-angiogenic and hypoxia-targeting strategies, has been limited. This review will explore the hypothesis that the TME of MM engrafted in the BM is distinctly different from non-hematological-derived solid tumors calling into question how effective these strategies may be against MM. We further identify other hypoxia-mediated effectors, such as hypoxia-mediated acidification of the TME, oxygen-dependent metabolic changes, and the generation of reactive oxygen species (ROS), that may prove to be more effective targets against MM.

【 授权许可】

Unknown