Targeting Mcl-1 and Other Bcl-2 Family Member Proteins in Cancer Therapy

Publication date: Available online 19 October 2018Source: Pharmacology &TherapeuticsAuthor(s): Ryuji Yamaguchi, Lydia Lartigue, Guy PerkinsAbstractRegulation of both the extrinsic and the mitochondria-dependent intrinsic apoptotic pathways plays a key role in the development of the hematopoietic system, for sustaining cell survival during generation of various cell types, in eliminating cells with dual identities such as CD4/CD8 double-positive cells1,2, for sustaining cells during the rapid clonal expansion phase3, as well as eliminating cells during the contraction phase4. The anti-apoptotic protein Mcl-1 is necessary for sustaining hematopoietic stem cells (HPS)5,6. The anti-apoptotic factors Mcl-1, Bcl-2, and Bcl-xL were also found to be over-expressed in acute myeloid leukemia (AML)7 and acute lymphocytic leukemia (ALL)8, suggesting that dis-regulated apoptotic processes could be a factor in the instigation of leukemia and/or its relapse. Molecules targeting these proteins were used as single agents to treat leukemia. However, by using a set of recently developed specific molecule inhibitors targeting anti-apoptotic proteins, distinct roles are being discovered for these anti-apoptotic proteins during hematopoietic and tumor development. Furthermore, using these inhibitors in proper combinations can effectively induce apoptosis in various solid tumors, even though each agent on its own cannot induce apoptosis in them. These new findings suggest that inhibiting anti-a...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research

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AbstractSkeletal muscle atrophy and loss of adipose tissue, referred to as sarcopenia and adipopenia, respectively, are often observed in cancer patients. We investigated the impact of sarcopenia and adipopenia on clinical outcomes in 90 adult patients with newly diagnosed acute myeloid leukemia (AML) who received induction chemotherapy. Computed tomography (CT) before treatment revealed sarcopenia in 39 patients (43%) and adipopenia in 35 patients (39%). We analyzed the treatment efficacy of induction chemotherapy and survival outcomes. Three-year overall survival (OS) was 35% in the sarcopenic group and 67% in the non-sa...
Source: Annals of Hematology - Category: Hematology Source Type: research
(Tokyo Medical and Dental University) Tokyo Medical and Dental University (TMDU) researchers used knockout mouse models created by gene editing to reveal that the miRNA miR-146b, like miR-146a, is involved in the development of cancers, with them having similar but not identical effects. The knockout mice showed high rates of B-cell lymphoma and acute myeloid leukemia, which was associated with the absence of miRNA causing NF-κB overactivation. These insights should help in the fight against cancers involving miRNA dysregulation.
Source: EurekAlert! - Biology - Category: Biology Source Type: news
As Tyler Bacon gripped the lectern in Carnesale Commons and scanned the crowd gazing at him expectantly, he struggled to hold back tears.The 39-year-old father of two from Thousand Oaks was finally meeting some of the more than two dozen people whose blood and platelet donations sustained his life during cancer treatment at  Ronald Reagan UCLA Medical Center.  “Because you showed up and donated, my parents still have a son,” Bacon said. “My children have a dad. My wife has a husband.”His voice quaking with emotion, he added, “All the gratitude in the world would not be enough to say ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
As Tyler Bacon gripped the lectern in Carnesale Commons and scanned the crowd gazing at him expectantly, he struggled to hold back tears.The 39-year-old father of two from Thousand Oaks was finally meeting some of the more than two dozen people whose blood and platelet donations sustained his life during cancer treatment at  Ronald Reagan UCLA Medical Center.  “Because you showed up and donated, my parents still have a son,” Bacon said. “My children have a dad. My wife has a husband.”His voice quaking with emotion, he added, “All the gratitude in the world would not be enough to say ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Specific MCL-1 inhibitor kills multiple myeloma and acute myeloid leukemia cells.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Editors ' Choice Source Type: research
Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?, Published online: 16 January 2019; doi:10.1038/s41408-019-0170-3Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?
Source: Blood Cancer Journal - Category: Hematology Authors: Source Type: research
The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia, Published online: 15 January 2019; doi:10.1038/s41408-018-0169-1The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia
Source: Blood Cancer Journal - Category: Hematology Authors: Source Type: research
AbstractBackgroundSocial isolation potentiates the risk of death by cancer in the older cancer patient population. The PREDOMOS study investigates the impact of establishing a Program of Social intervention associated with techniques of Domotic and Remote assistance on the improvement of quality of life of older isolated patients, treated for locally advanced or metastatic cancer. This paper updates the pilot trial protocol.Methods/designThe original protocol was published in Trials, accessible athttps://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-1894-7.This update reports on the eligibility criteria expan...
Source: Trials - Category: Research Source Type: clinical trials
A new study published in Cancer compared ELN-2017 to ELN-2010 in terms of distinguishing prognosis in younger patients with newly diagosed AML.
Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
Following publication of the original article [1], we have been notified that the data in Fig. 1 was wrongly presented. The correct Fig. 1 is presented below.
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Correction Source Type: research
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