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https://www.readbyqxmd.com/read/27894203/management-of-adverse-events-induced-by-next-generation-immunomodulatory-drug-and-proteasome-inhibitors-in-multiple-myeloma
#1
Marco Salvini, Francesca Bonello, Mario Boccadoro, Alessandra Larocca
In the last decade the introduction of novel agents has strongly improved multiple myeloma prognosis by doubling median overall survival. Unfortunately disease relapse is very common and patients may become refractory to previous drugs. Therefore, new therapeutic strategies are urgently needed. Areas covered. We have reviewed the available data on next generation novel agents, particularly immunomodulatory drug pomalidomide and proteasome inhibitors carfilzomib and ixazomib, the latter being the first-in-class orally available...
November 29, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27888768/multiple-myeloma-treatment-at-relapse-after-autologous-stem-cell-transplantation-a-practical-analysis
#2
REVIEW
F Malard, J L Harousseau, M Mohty
Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse...
November 15, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27888016/post-transplantation-cyclophosphamide-and-ixazomib-combination-rescues-mice-subjected-to-experimental-gvhd-and-is-superior-to-either-agent-alone
#3
A Samer Al-Homsi, Austin Goodyke, Michael McLane, Sarah Abdel-Mageed, Kelli Cole, Marlee Muilenburg, Yuxin Feng
Lapses in the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) warrants novel approaches. Such approaches include, among others, the use of post-transplantation cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently produces low rates of chronic GvHD, the incidence of acute GvHD remains significant. Inversely, prolonged post-transplantation administration of proteasome inhibitors carries a risk of paradoxical aggravation of GvHD...
November 22, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27863374/magic-year-for-multiple-myeloma-therapeutics-key-takeaways-from-the-ash-2015-annual-meeting
#4
REVIEW
Kejie Zhang, Aakash Desai, Dongfeng Zeng, Tiejun Gong, Peihua Lu, Michael Wang
Despite the availability of various anticancer agents, Multiple Myeloma (MM) remains incurable in most cases, along with high relapse rate in the patients treated with these agents. The year 2015 saw major advancements in our battle against multiple myeloma. In 2015, the U.S. Food and Drug Administration (FDA) approved three new therapies for multiple myeloma, namely Ixazomib (an oral proteasome inhibitor), Daratumumab and Elotuzumab (monoclonal antibodies against CD38 and SLAMF7 respectively). The purpose of this review is to provide a detailed analysis of these aforementioned breakthrough therapies and two other newer agents, Filanesib (kinesis spindle inhibitor) and selinexor (SINE inhibitor), presented at the 2015 annual meeting of American Society of Hematology (ASH)...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27859518/ixazomib-cardiotoxicity-a-possible-class-effect-of-proteasome-inhibitors
#5
Hayan Jouni, Mary C Aubry, Martha Q Lacy, S Vincent Rajkumar, Shaji K Kumar, Robert L Frye, Joerg Herrmann
No abstract text is available yet for this article.
November 17, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27795518/current-treatment-of-refractory-and-relapsed-multiple-myeloma
#6
Makoto Sasaki
In the past decade, previously approved novel agents, such as proteasome inhibitors (bortezomib) and immunomodulatory drugs ([IMiDs]; e.g., lenalidomide), have led to significant improvement in the treatment of multiple myeloma in Japan. However, almost all patients will ultimately relapse, even when they have achieved a deep and prolonged therapeutic response with initial treatment. Next-generation IMiDs (pomalidomide) and deacetylase inhibitors (panobinostat) were approved for use as salvage therapy for refractory and relapsed multiple myeloma [RRMM] within the last year...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27783987/the-combination-of-mln2238-ixazomib-with-interferon-alpha-results-in-enhanced-cell-death-in-melanoma
#7
Lorena P Suarez-Kelly, Gregory M Kemper, Megan C Duggan, Andrew Stiff, Tiffany C Nole, Joseph Markowitz, Eric A Luedke, Vedat O Yildiz, Lianbo Yu, Alena Cristina Jaime-Ramirez, Volodymyr Karpa, Xiaoli Zhang, William E Carson
The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27782060/identification%C3%A2-of%C3%A2-long%C3%A2-non-coding%C3%A2-rnas-deregulated%C3%A2-in%C3%A2-multiple%C3%A2-myeloma%C3%A2-cells%C3%A2-resistant%C3%A2-to-proteasome%C3%A2-inhibitors
#8
Ehsan Malek, Byung-Gyu Kim, James J Driscoll
While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance...
October 6, 2016: Genes
https://www.readbyqxmd.com/read/27702799/randomized-phase-2-trial-of-ixazomib-and-dexamethasone-in-relapsed-multiple-myeloma-not-refractory-to-bortezomib
#9
Shaji K Kumar, Betsy R LaPlant, Craig B Reeder, Vivek Roy, Alese E Halvorson, Francis Buadi, Morie A Gertz, P Leif Bergsagel, Angela Dispenzieri, Melanie A Thompson, Jamie Crawley, Prashant Kapoor, Joseph Mikhael, Keith Stewart, Suzanne R Hayman, Yi L Hwa, Wilson Gonsalves, Thomas E Witzig, Sikander Ailawadhi, David Dingli, Ronald S Go, Yi Lin, Candido E Rivera, S Vincent Rajkumar, Martha Q Lacy
Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations. The current trial was designed to examine the efficacy and toxicity of combining 2 different doses of ixazomib (4 mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, in relapsed myeloma...
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27687684/novel-proteasome-inhibitor-ixazomib-sensitizes-neuroblastoma-cells-to-doxorubicin-treatment
#10
Haoyu Li, Zhenghu Chen, Ting Hu, Long Wang, Yang Yu, Yanling Zhao, Wenijing Sun, Shan Guan, Jonathan C Pang, Sarah E Woodfield, Qing Liu, Jianhua Yang
Neuroblastoma (NB) is the most common extracranial malignant solid tumor seen in children and continues to lead to the death of many pediatric cancer patients. The poor outcome in high risk NB is largely attributed to the development of chemoresistant tumor cells. Doxorubicin (dox) has been widely employed as a potent anti-cancer agent in chemotherapeutic regimens; however, it also leads to chemoresistance in many cancer types including NB. Thus, developing novel small molecules that can overcome dox-induced chemoresistance is a promising strategy in cancer therapy...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27675012/bh3-mimetic-abt-737-sensitizes-colorectal-cancer-cells-to-ixazomib-through-mcl-1-downregulation-and-autophagy-inhibition
#11
L Yang
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27673290/the-role-of-high-dose-melphalan-and-autologous-stem-cell-transplant-in-the-rapidly-evolving-era-of-modern-multiple-myeloma-therapy
#12
Peter M Voorhees, Saad Z Usmani
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma...
September 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27668055/ninlaro-ixazomib-first-oral-proteasome-inhibitor-approved-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma
#13
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
https://www.readbyqxmd.com/read/27659429/stem-cell-transplantation-in-multiple-myeloma
#14
Massimo Offidani, Silvia Gentili, Francesca Gay, Elena Aghemo, Laura Maracci, Laura Corvatta, Antonio Palumbo
High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT. Moreover, the positive results obtained with these agents in consolidation and maintenance strategies after ASCT strongly support the concept of continuous therapy, whose ultimate goal is the long-term control of the disease and the improvement of outcome...
September 19, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27650125/treatment-options-for-relapse-after-autograft-in-multiple-myeloma-report-from-an-ebmt-educational-meeting
#15
Laurent Garderet, Gordon Cook, Holger W Auner, Benedetto Bruno, Henk Lokhorst, Jose Antonio Perez-Simon, Firoozeh Sahebi, Christof Scheid, Curly Morris, Anja van Biezen, Mohamad Sobh, Mauricette Michallet, Gösta Gahrton, Stefan Schönland, Nicolaus Kröger
Major improvements have been made in the treatment of myeloma. However, all patients, perhaps with some exceptions, eventually relapse, even after autologous stem cell transplantation (ASCT). In that setting, the combinations of new drugs, namely the IMiDs and the proteasome inhibitors along with steroids, give encouraging results in relapsed patients. The median progression-free survival (PFS) is 20 months with lenalidomide plus dexamethasone plus ixazomib and 26 months with lenalidomide plus dexamethasone plus carfilzomib...
September 21, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27647123/proteasome-inhibitors-in-al-amyloidosis-focus-on-mechanism-of-action-and-clinical-activity
#16
T Jelinek, E Kryukova, Z Kufova, F Kryukov, R Hajek
Proteasome inhibitors are the backbone in the treatment of multiple myeloma with 3 of its representatives (bortezomib, carfilzomib, and ixazomib) having already been approved. There is a different situation altogether in the treatment of amyloid light chain (AL) amyloidosis where owing to the rarity of this entity neither of these drugs has currently gained approval. Amyloid light chain plasma cells are possibly more vulnerable to bortezomib than myeloma plasmocytes because of a slightly distinct mechanism of action, which is described in depth in this manuscript...
September 20, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27604794/recent-advances-in-multiple-myeloma-a-korean-perspective
#17
REVIEW
Junshik Hong, Jae Hoon Lee
Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab...
September 2016: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/27529620/activation-of-chymotrypsin-like-activity-of-the-proteasome-during-ischemia-induces-myocardial-dysfunction-and-death
#18
Gina Sanchez, Daniela Berrios, Ivonne Olmedo, Javier Pezoa, Jaime A Riquelme, Luis Montecinos, Zully Pedrozo, Paulina Donoso
Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination...
2016: PloS One
https://www.readbyqxmd.com/read/27471867/new-investigational-drugs-with-single-agent-activity-in-multiple-myeloma
#19
REVIEW
A M Rajan, S Kumar
The treatment of multiple myeloma (MM) is rapidly evolving. In the United States, four drugs (panobinostat, ixazomib, daratumumab and elotuzumab) were approved for the treatment of MM in 2015. As a result of improved diagnosis and therapy, there has been a dramatic improvement in the outcome of MM in the last decade, probably more than any other malignancy. Numerous agents continue to be studied in preclinical models and in clinical trials, with many demonstrating clinical efficacy that appears promising enough to have a trajectory for regulatory approval...
July 29, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27438821/computational-approaches-for-the-discovery-of-human-proteasome-inhibitors-an-overview
#20
REVIEW
Romina A Guedes, Patrícia Serra, Jorge A R Salvador, Rita C Guedes
Proteasome emerged as an important target in recent pharmacological research due to its pivotal role in degrading proteins in the cytoplasm and nucleus of eukaryotic cells, regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription, immune response, and signaling processes. The last two decades witnessed intensive efforts to discover 20S proteasome inhibitors with significant chemical diversity and efficacy. To date, the US FDA approved to market three proteasome inhibitors: bortezomib, carfilzomib, and ixazomib...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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