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Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma.

ABSTRACT: Multiple myeloma (MM) is the second most common hematological malignancy, characterized by an abnormal accumulation of plasma cells in the bone marrow. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of multiple genes to regulate various principal biological functions, for example, cell proliferation and survival, stemness, inflammation and immune responses. Aberrant STAT3 activation has been identified as a key driver of tumorigenesis in many types of cancers, including MM. Herein, we summarize the current evidence for the role of STAT3 in affecting cancer hallmark traits by: (1) sustaining MM cell survival and proliferation, (2) regulating tumor microenvironment, (3) inducing immunosuppression. We also provide an update of different strategies for targeting STAT3 in MM with special emphasis on JAK inhibitors that are currently undergoing clinical trials. Finally, we discuss the challenges and future direction of understanding STAT3 signaling in MM biology and the clinical development of STAT3 inhibitors.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8946161 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma.

Zhou Jianbiao J Chng Wee-Joo WJ

Cells 20220310 6

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by an abnormal accumulation of plasma cells in the bone marrow. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of multiple genes to regulate various principal biological functions, for example, cell proliferation and survival, stemness, inflammation and immune responses. Aberrant STAT3 activation has been identified as a key dr ...[more]

PMID: 35326392

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Project description:Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. It is an oral, multitargeted inhibitor of receptor tyrosine kinases, including BCR-ABL, c-KIT, PDGFR, and Src family kinases. However, little is known about the effects of radotinib on multiple myeloma cells. However, little is known about the effects of radotinib on multiple myeloma cells. But even tinip almost not known about the impact of multiple myeloma cells. Moreover, nothing is known about how it affects STAT3 and JAK2. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Herein, Moreover, nothing is known about how it. Moreover, not all is known about how the affects STAT3 and JAK2. We investigated the effect of radotinib on the STAT3 signaling pathway in MM cells, including several MM cell lines and mouse models. So we investigated the effect of radotinib on MM cells, including several MM cell lines and mouse models. Interestingly, radotinib induced apoptosis, and inhibited cell proliferation in MM cells including RPMI-8226, MM.1S, U266B1, and IM-9 cells. Moreover, radotinib treatment significantly increased the number Annexin V-positive cells and G0/G1-phase cells. In addition, radotinib treatment in various MM cells strongly suppressed the activity and expression of STAT3 and JAK2 proteins. We also observed that diverse proteins related to the STAT3 signaling pathway, including c-Myc, Bcl-xL, Mcl-1, cyclin D1 and cyclin D3, were powerfully inhibited by radotinib treatment in MM cells. Furthermore, radotinib significantly suppressed MM cell growth in a xenograft animal model using IM-9 cells. In conclusion, radotinib may play an important role as a candidate agent for MM treatment.

Dataset Information

Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma.

Publications

Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma.

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