scholarly journals New Frontiers in the Treatment of Multiple Myeloma

2006 ◽  
Vol 6 ◽  
pp. 1475-1503 ◽  
Author(s):  
Janice Jin Hwang ◽  
Irene M. Ghobrial ◽  
Kenneth C. Anderson
Keyword(s):  
Multiple Myeloma ◽  
Intracellular Signaling ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Clinical Settings ◽  
New Agents ◽  
Surface Receptors ◽  
Intracellular Signaling Pathways ◽  
Significant Efficacy ◽  
Clinical Responses

Recent leaps in elucidating the biology of myeloma, particularly the intracellular pathways and the complex interaction with the bone marrow microenvironment, have resulted in an unprecedented surge of novel, targeted therapies and therapeutic regimens. There are currently over 30 new agents being tested in the treatment of multiple myeloma (MM). Many of these are novel, targeted agents that have demonstrated significant efficacy and prolonged survival. In this review, we summarize the current understanding of the mechanisms of action of novel therapies being tested in the preclinical and clinical settings in MM. These include agents that act directly on the intracellular signaling pathways, cell maintenance processes, and cell surface receptors. Finally, we present the clinical responses to some of these agents when used alone or in combination in clinical trials of patients with MM. Indeed, MM has become a model disease for the development of novel, therapeutic agents.

scholarly journals New Insights in Anti-Angiogenesis in Multiple Myeloma

2018 ◽  
Vol 19 (7) ◽  
pp. 2031 ◽  
Author(s):  
Domenico Ribatti ◽  
Angelo Vacca
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Recent Literature ◽  
Therapeutic Agents ◽  
Bone Marrow Microenvironment ◽  
Clinical Settings ◽  
Preclinical Models ◽  
Direct Production ◽  
Angiogenic Cytokines

Angiogenesis is a constant hallmark of multiple myeloma (MM) progression and involves direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment. This article summarizes the more recent literature data concerning the employment of anti-angiogenic therapeutic agents actually used in preclinical models and clinical settings for the treatment of multiple myeloma.

scholarly journals Targeted Therapy in Multiple Myeloma

2005 ◽  
Vol 12 (2) ◽  
pp. 91-104 ◽  
Author(s):  
Wee Joo Chng ◽  
Lee Gong Lau ◽  
Noorainun Yusof ◽  
Benjamin M. F. Mow
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Intracellular Signaling ◽  
Resistance Mechanism ◽  
Growth Factor Receptor ◽  
Therapeutic Agents ◽  
Farnesyltransferase Inhibitors ◽  
Antisense Gene ◽  
Novel Therapeutic

Background: Multiple myeloma (MM) is an incurable malignancy. Recent insights into its biology has allowed the use of novel therapies targeting not only the deregulated intracellular signaling in MM cells but also its interaction with the bone marrow microenvironment that confers drug resistance, growth, and survival advantage to the malignant cells. Methods: We review and summarize the recent advances in our knowledge of myeloma biology as well as the mechanism of action and clinical efficacy for novel therapeutic agents in clinical trials. Results: Several novel therapeutic agents are currently in clinical trials. Thalidomide is already established for both initial and salvage treatment. Bortezomib is being tested alone and in combination with conventional chemotherapy in various settings. Other agents are less effective in producing response but have been able to stabilize disease in patients with relapsed and/or refractory disease, such as arsenic trioxide, farnesyltransferase inhibitors, 2-methoxyestradiol, and vascular endothelial growth factor receptor inhibitors. Insights into drug resistance mechanism have also led to the development of novel agents that sensitize myeloma cells to chemotherapy (Bcl-2 antisense). Gene expression studies have in many instances identified pathways other than the intended target of the drug and have provided insights into the therapeutic mechanisms. Conclusions: In the future, patients with MM will have more therapeutic options available than ever before. The challenge will be to identify patient subgroups that will benefit most from the different therapies and then determine how these biologically based therapies could be combined and incorporated into the overall management of patients.

scholarly journals How I treat myeloma with new agents

Blood ◽  
2017 ◽  
Vol 130 (13) ◽  
pp. 1507-1513 ◽  
Author(s):  
Philippe Moreau
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Histone Deacetylase Inhibitors ◽  
Treatment Options ◽  
Proteasome Inhibitors ◽  
Mechanisms Of Action ◽  
Third Generation ◽  
New Agents ◽  
Immunomodulatory Agents ◽  
The Third

Abstract At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs), and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second-generation PIs carfilzomib and ixazomib, the DACI panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines, and have transformed our approach to the treatment of patients. These agents may be part of doublet or triplet combinations, or incorporated into intensive strategies with autologous stem cell transplantation. In this review, I discuss the different treatment options available today for the treatment of MM in frontline and relapse settings.

scholarly journals Role of PI3K in the Progression and Regression of Atherosclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunyun Zhao ◽  
Yongjiang Qian ◽  
Zhen Sun ◽  
Xinyi Shen ◽  
Yaoyao Cai ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Immune Disorders ◽  
Regulatory Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Surface Receptors ◽  
Extracellular Signals ◽  
Intracellular Signaling Pathways ◽  
Pi3k Activity

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

scholarly journals AMPK Activity: A Primary Target for Diabetes Prevention with Therapeutic Phytochemicals

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4050
Author(s):  
Min-Yu Chung ◽  
Hyo-Kyoung Choi ◽  
Jin-Taek Hwang
Keyword(s):  
Metabolic Syndrome ◽  
Intracellular Signaling ◽  
Blood Glucose Control ◽  
Mechanisms Of Action ◽  
Primary Target ◽  
Intracellular Signaling Pathways ◽  
Ancient Times ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Diabetes is a metabolic syndrome characterized by inadequate blood glucose control and is associated with reduced quality of life and various complications, significantly shortening life expectancy. Natural phytochemicals found in plants have been traditionally used as medicines for the prevention of chronic diseases including diabetes in East Asia since ancient times. Many of these phytochemicals have been characterized as having few side effects, and scientific research into the mechanisms of action responsible has accumulated mounting evidence for their efficacy. These compounds, which may help to prevent metabolic syndrome disorders including diabetes, act through relevant intracellular signaling pathways. In this review, we examine the anti-diabetic efficacy of several compounds and extracts derived from medicinal plants, with a focus on AMP-activated protein kinase (AMPK) activity.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

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