Challenge for identifying specific hypoxia-inducible genes as novel therapeutic targets in multiple myeloma

Abstract

Multiple myeloma (MM) is a refractory hematological malignant neoplasm derived from plasma cells. It has been extensively studied in the quest to develop treatment strategies. Furthermore, several factors of the bone marrow microenvironment could be candidates for novel therapeutic targets. Among these, the hypoxic response is the most important factor maintaining cell homeostasis, and is generally considered as a therapeutic target for various cancers including MM. Although oxygen partial pressure of bone marrow is 50–55 mmHg, that of hypoxic niche is less than 10 mmHg. Myeloma cells adapting to the hypoxic niche exhibit changes in gene expression via activation of hypoxia-inducible factor (HIF), and subsequently acquiring treatment resistance. However, because of its negative effects on normal cells and tissues, HIF inhibitor is not used in medical practice. Hence, downstream targets of HIF should be investigated. In particular, changes induced by the hypoxic response, such as metabolic pathways, cell dissemination, and malignant bone marrow environment, may be promising therapeutic targets. Therefore, future studies should focus on identifying therapeutic drugs targeting hypoxic environments and hypoxia-inducible genes.