Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents.

Cells

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Published: April 2019

Chemotherapeutic targeting of microtubules has been the standard of care in treating a variety of malignancies for decades. During mitosis, increased microtubule dynamics are necessary for mitotic spindle formation and successful chromosomal segregation. Microtubule targeting agents (MTAs) disrupt the dynamics necessary for successful spindle assembly and trigger programmed cell death (apoptosis). As the critical regulators of apoptosis, anti-apoptotic BCL2 family members are often amplified during carcinogenesis that can result in MTA resistance. This review outlines how BCL2 family regulation is positioned within the context of MTA treatment and explores the potential of combination therapy of MTAs with emerging BCL2 family inhibitors.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523793PMC
http://dx.doi.org/10.3390/cells8040346DOI Listing

Publication Analysis

Top Keywords

bcl2 family
16
microtubule targeting
8
targeting agents
8
regulating bcl2
4
family
4
family improve
4
improve sensitivity
4
sensitivity microtubule
4
agents chemotherapeutic
4
chemotherapeutic targeting
4

Similar Publications

Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.

View Article and Find Full Text PDF

Genome-wide CRISPR-Cas 9 screens identify BCL family members as modulators of response to regorafenib in experimental glioma.

Neuro Oncol

January 2025

Department of Neurology & Interdisciplinary Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Eberhard Karls University Tübingen; Tübingen, Germany.

Background: Registered systemic treatment options for glioblastoma patients are limited. The phase II REGOMA trial suggested an improvement of median overall survival in progressive glioblastoma by the multi-tyrosine kinase inhibitor regorafenib. This has not been confirmed by GBM AGILE.

View Article and Find Full Text PDF

Nobiletin: a potential erythropoietin receptor activator protects renal cells against hypoxia.

Apoptosis

January 2025

Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.

Tangerine peel is a traditional Chinese herb and has been widely applied in foods and medicine for its multiple pharmacological effects. Erythropoietin receptor (EPOR), a member of the cytokine receptor family, is widely expressed in multiple tissues in especial kidney and plays protective effects in adverse physiological and pathological conditions. We hypothesized that it might be EPOR agonists existing in Tangerine peel bring such renal benefits.

View Article and Find Full Text PDF

Purpose: The incidence of vascular dementia (VaD), as one of the main types of dementia in old age, has been increasing year by year, and exploring its pathogenesis and seeking practical and effective treatment methods are undoubtedly the key to solving this problem. Phosphoglycerate translocase 5 (PGAM5), as a crossroads of multiple signaling pathways, can lead to mitochondrial fission, which in turn triggers the onset and development of necroptosis, and thus PGAM5 may be a novel target for the prevention and treatment of vascular dementia.

Methods: Animal model of vascular dementia was established by Two-vessel occlusion (2-VO) method, and cellular model of vascular dementia was established by oxygen glucose deprivation (OGD) method.

View Article and Find Full Text PDF

Heat stress poses a significant challenge for maize production, especially during the spring when high temperatures disrupt cellular processes, impeding plant growth and development. The B-cell lymphoma-2 (Bcl-2) associated athanogene (BAG) gene family is known to be relatively conserved across various species. It plays a crucial role as molecular chaperone cofactors that are responsible for programmed cell death and tumorigenesis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!