type: misc

label: url

en: ダラツムマブ・ボルヒアルロニダーゼ アルファ配合(ダラキューロ)

ja: ダラツムマブ・ボルヒアルロニダーゼ アルファ配合(ダラキューロ)

en: がん最新の薬物療法 2023-2024

ja: がん最新の薬物療法 2023-2024


en: Myeloma-Bone Interaction: A Vicious Cycle via TAK1-PIM2 Signaling

en: Multiple myeloma (MM) has a propensity to develop preferentially in bone and form bone-destructive lesions. MM cells enhance osteoclastogenesis and bone resorption through activation of the RANKL-NF-κB signaling pathway while suppressing bone formation by inhibiting osteoblastogenesis from bone marrow stromal cells (BMSCs) by factors elaborated in the bone marrow and bone in MM, including the soluble Wnt inhibitors DKK-1 and sclerostin, activin A, and TGF-β, resulting in systemic bone destruction with loss of bone. Osteocytes have been drawn attention as multifunctional regulators in bone metabolism. MM cells induce apoptosis in osteocytes to trigger the production of factors, including RANKL, sclerostin, and DKK-1, to further exacerbate bone destruction. Bone lesions developed in MM, in turn, provide microenvironments suited for MM cell growth/survival, including niches to foster MM cells and their precursors. Thus, MM cells alter the microenvironments through bone destruction in the bone where they reside, which in turn potentiates tumor growth and survival, thereby generating a vicious loop between tumor progression and bone destruction. The serine/threonine kinases PIM2 and TAK1, an upstream mediator of PIM2, are overexpressed in bone marrow stromal cells and osteoclasts as well in MM cells in bone lesions. Upregulation of the TAK1-PIM2 pathway plays a critical role in tumor expansion and bone destruction, posing the TAK1-PIM2 pathway as a pivotal therapeutic target in MM.

en: Cancers

ja: Cancers


en: Histone deacetylase inhibitors in multiple myeloma: from bench to bedside

en: Histone deacetylases (HDACs) deacetylate the lysine residues of both histones and non-histone proteins. Histone acetylation results in a loose local chromatin structure that regulates gene-specific transcription. Non-histone proteins can also be acetylated, leading to dynamic changes in their activity and stability. For these reasons, HDAC inhibition has emerged as a potential approach for the treatment of MM. Specifically, combination treatment with HDAC inhibitors and proteasome inhibitors or immunomodulatory drugs shows remarkable anti-MM activity in both preclinical and clinical settings. However, the clinical studies using non-selective HDAC inhibitors also cause unfavorable side effects in patients, leading us to develop more isoform- and/or class-selective HDAC inhibitors to enhance tolerability without diminishing anti-MM activity, thereby improving patient outcome in MM.

en: International Journal of Hematology

ja: International Journal of Hematology