Bcl-2 inhibition in the treatment of hematologic malignancies DOI Creative Commons

John X Wei,

Marina Konopleva

Frontiers in Hematology, Journal Year: 2023, Volume and Issue: 2

Published: Dec. 4, 2023

Apoptosis is a tightly regulated process of cell death occurring through extrinsic and intrinsic pathways. The Bcl-2 family proteins implicated in the pathway encompasses both pro-apoptotic anti-apoptotic proteins. Anti-apoptotic are frequently overexpressed hematologic malignancies so inhibitors have been developed to combat these malignancies. first so-far only FDA-approved inhibitor has venetoclax, initially for treatment chronic lymphocytic leukemia (CLL) with 17-p deletion as second-line agent, followed by later expansion all CLL selected acute myeloid (AML) indications. Venetoclax other members demonstrated significant potential. However, their use requires careful consideration disease indication, along biomarkers associated optimal drug combinations. Side-effect profiles specific patterns resistance must be considered well. In this review, we examine detail characteristics role apoptosis. We discuss development that led first-in-class approval relevant considerations. Finally, future directions domain pharmaceutical development.

Language: Английский

Contribution of tumor microenvironment (TME) to tumor apoptosis, angiogenesis, metastasis, and drug resistance DOI
Yanhong Xiao, M Hassani,

Melina Barahouei Moghaddam

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 14, 2025

Language: Английский

Citations

3
Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution—Diving into Microglia/Macrophage Functions and Therapeutic Modality DOI

Xiaoqiang Xie,

Shan‐Shan Dong, Ru‐Juan Liu

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7583 - 7602

Published: Feb. 27, 2024

Language: Английский

Citations

8
Hijacking homeostasis: Regulation of the tumor microenvironment by apoptosis DOI Creative Commons
Christopher D. Gregory

Immunological Reviews, Journal Year: 2023, Volume and Issue: 319(1), P. 100 - 127

Published: Aug. 8, 2023

Cancers are genetically driven, rogue tissues which generate dysfunctional, obdurate organs by hijacking normal, homeostatic programs. Apoptosis is an evolutionarily conserved regulated cell death program and a profoundly important mechanism that common (alongside tumor proliferation) in actively growing cancers, as well tumors responding to cytotoxic anti-cancer therapies. Although known for its cell-autonomous tumor-suppressive qualities, apoptosis harbors pro-oncogenic properties deployed through non-cell-autonomous mechanisms generally remain poorly defined. Here, the roles of biology reviewed, with particular focus on secreted fragmentation products apoptotic cells their effects tumor-associated macrophages, key supportive aberrant homeostasis microenvironment. Historical aspects loss growth kinetics considered impact (and potential impact) apoptotic-cell clearance (efferocytosis) released soluble extracellular vesicle-associated factors discussed from perspectives inflammation, tissue repair, regeneration An "apoptosis-centric" view proposed dying provide platform intricate intercellular communication networks cancers. The perspective has implications future research improving cancer diagnosis therapy.

Language: Английский

Citations

13
C-reactive protein-induced injury in Mycoplasma pneumoniae -infected lung epithelial cells is mediated by the P38 MAPK/mitochondrial apoptosis pathway DOI Creative Commons

Lianjia Li,

Yang Zhang, Zhao Lin

et al.

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Patients with Mycoplasma pneumoniae (MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. levels were assessed in children diagnosed pneumonia (MPP) and A549 cells infected MP. genetically modified overexpress CRP. Effects on viability, apoptosis, reactive oxygen species (ROS) mitochondrial membrane potential (ΔΨm) evaluated. The expression of proteins implicated the p38 MAPK/mitochondrial apoptotic pathway was analyzed. protective effects MAPK inhibitor SB203580 protector cyclosporin A (CsA) assessed. elevated both MPP patients MP-infected compared controls. Increased apoptosis reduced viability observed cells. overexpression led upregulation pathway, increased cytoplasmic Cyt C, decreased Tom 20 ΔΨm, ROS. Pretreatment or posttreatment CsA damage enhanced survival. during infection promote by activating pathway. Targeting this could offer therapeutic reduce patients.IMPORTANCEThis study provides critical information understanding pathophysiological mechanisms for concerning mediating injury. This outlines significant increase shows its direct involvement through By explaining possibility targeting connected signaling devise interventions amelioration is brought light. implications such data are not merely added knowledge disease pathobiology but also it brings new promise novel intervention strategies result improved clinical outcomes. elucidation specific molecular targets inside heralds a area regarding direction future research application humanity general broader relevance impact respiratory diseases.

Language: Английский

Citations

0
Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response DOI Creative Commons
Parastoo Shahrouzi, Youness Azimzade, Wioletta Brankiewicz

et al.

Breast Cancer Research, Journal Year: 2024, Volume and Issue: 26(1)

Published: Nov. 27, 2024

Abstract Breast cancer (BCa) is a major global health challenge. The BCa genome often carries extensive somatic copy number alterations (CNAs), including gains/amplifications and losses/deletions. These CNAs significantly affect tumor development, drug response patient survival. However, how individual contribute mostly elusive. We identified loss of chromosome 13q14.2 as key CNA in BCa, occurring up to 63% patients, depending on the subtype, correlating with poor Through multi-omics vitro analyses, we uncover paradoxical role loss, promoting both cell cycle pro-apoptotic pathways cells, while also associating increased NK macrophage populations microenvironment. Notably, increases susceptibility BCL2 inhibitors, patient-derived xenografts. Thus, could serve biomarker for prognosis treatment, potentially improving outcomes patients. Graphical abstract

Language: Английский

Citations

2
OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer DOI Open Access
Spiros Vlahopoulos, Lang Pan, Lokman Varışlı

et al.

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 148 - 148

Published: Dec. 28, 2023

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes first step in DNA base excision repair pathway, is now also recognized a modulator of gene expression. What important for cancer OGG1 acts NFκB-driven Specifically, oxidant stress cell transiently halts enzymatic activity substrate-bound OGG1. The stalled facilitates binding transactivators, such NFκB to their cognate sites, enabling expression cytokines and chemokines, with ensuing recruitment inflammatory cells. Recently, we highlighted chief aspects involvement regulation expression, hold significance lung development. However, has been implicated molecular underpinning acute myeloid leukemia. This review analyzes discusses how these cells adapt through redox-modulated intricate connections, via interaction NFκB, provides malignant alternative pathways transform microenvironment, adjustment, promoting proliferation, metastasis, evading killing by therapeutic agents.

Language: Английский

Citations

5
OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer DOI Open Access

Spiros Angelou Vlahopoulos,

Lang Pan, Lokman Varışlı

et al.

Published: Nov. 23, 2023

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes first step in DNA base excision repair pathway, is now known also a modulator of gene expression. What important for cancer, OGG1 acts NFκB-driven Specifically, oxidant stress cell transiently halts enzymatic activity substrate-bound OGG1. The stalled facilitates binding transactivators, including NFκB, to their cognate sites enable expression cytokines and chemokines, with ensuing recruitment inflammatory cells. Recently, we highlighted chief aspects involvement regulation expression, have significance lung cancer development. However, has been implicated molecular underpinning acute myeloid leukemia. In general, capacity cells adapt oxidative depends on systems such interface bestows mechanism transformation its microenvironment adaptation survival malignant clones.

Language: Английский

Citations

4
Expression, purification and characterization of phosphatidylserine-targeting antibodies for biochemical and therapeutic applications DOI
Varsha Gadiyar, David Calianese,

Rachael Pulica

et al.

Methods in cell biology, Journal Year: 2024, Volume and Issue: unknown, P. 15 - 40

Published: Nov. 21, 2024

Language: Английский

Citations

1
Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response DOI Open Access
Parastoo Shahrouzi, Youness Azimzade, Wioletta Brankiewicz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 20, 2024

Breast cancer (BCa) is a major global health challenge, characterized by chromosomal instability (CIN) and subsequent acquisition of extensive somatic copy number alterations (CNAs). CNAs including amplifications deletions, significantly influence intra-tumor heterogeneity the tumor microenvironment (TME). Among these, loss chromosome 13q14.2 emerges as considerable factor in BCa pathogenesis treatment responses. We provide evidence that this genomic alteration under positive selective pressure, correlating with poorer patient survival. Furthermore, through multi-omic vitro analyses, we uncover dual role loss: it confers survival advantage to cells modulate cell cycle pro-apoptotic pathways cells, affecting macrophages population TME, while paradoxically increasing susceptibility BCL2 inhibitors. These findings suggest targeting biomarker could enhance efficacy existing treatments offer new avenue for improving clinical outcomes BCa. Abstract Figure 1. Graphical abstract

Language: Английский

Citations

1
Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response DOI
Parastoo Shahrouzi, Youness Azimzade, Wioletta Brankiewicz

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Abstract Breast cancer (BCa) is a major global health challenge, characterized by chromosomal instability (CIN) and subsequent acquisition of extensive somatic copy number alterations (CNAs). CNAs including amplifications deletions, significantly influence intra-tumor heterogeneity the tumor microenvironment (TME). Among these, loss chromosome 13q14.2 emerges as considerable factor in BCa pathogenesis treatment responses. We provide evidence that this genomic alteration under positive selective pressure, correlating with poorer patient survival.Furthermore, through multi-omic vitro analyses, we uncover dual role loss: it confers survival advantage to cells modulate cell cycle pro-apoptotic pathways cells, affecting macrophages population TME, while paradoxically increasing susceptibility BCL2 inhibitors. These findings suggest targeting biomarker could enhance efficacy existing treatments offer new avenue for improving clinical outcomes BCa.

Language: Английский

Citations

0