Targeting signaling pathways in prostate cancer: mechanisms and clinical trials DOI Creative Commons

Yundong He,

Weidong Xu,

Yu‐Tian Xiao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 24, 2022

Abstract Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment PCa continues improve. Recently, various new classes agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), poly(ADP-ribose) polymerase (PARP) (olaparib, rucaparib, talazoparib) have been developed treat PCa. Agents targeting other pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), epigenetic marks, successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) such as 177 Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy therapeutic efficacy. Advanced studies with immune checkpoint (ICIs) shown limited benefits PCa, whereas subgroups mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized targeted trials their underlying mechanisms, further discussed limitations future directions.

Language: Английский

Contextual determinants of TGFβ action in development, immunity and cancer DOI
Charles J. David, Joan Massagué

Nature Reviews Molecular Cell Biology, Journal Year: 2018, Volume and Issue: 19(7), P. 419 - 435

Published: April 11, 2018

Language: Английский

Citations

693

Fibroblasts: Origins, definitions, and functions in health and disease DOI Creative Commons
Maksim V. Plikus, Xiaojie Wang, Sarthak Sinha

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(15), P. 3852 - 3872

Published: July 1, 2021

Language: Английский

Citations

688

TGFβ biology in cancer progression and immunotherapy DOI
Rik Derynck, Shannon J. Turley, Rosemary J. Akhurst

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 18(1), P. 9 - 34

Published: July 24, 2020

Language: Английский

Citations

665

Specificity, versatility, and control of TGF-β family signaling DOI Open Access
Rik Derynck, Erine H. Budi

Science Signaling, Journal Year: 2019, Volume and Issue: 12(570)

Published: Feb. 26, 2019

Encoded in mammalian cells by 33 genes, the transforming growth factor-β (TGF-β) family of secreted, homodimeric and heterodimeric proteins controls differentiation most, if not all, cell lineages many aspects tissue physiology multicellular eukaryotes. Deregulation TGF-β signaling leads to developmental anomalies disease, whereas enhanced contributes cancer fibrosis. Here, we review fundamentals mechanisms that are initiated upon ligand binding its surface receptors dependence responses on input from cooperation with other pathways. We discuss how exquisitely control functional presentation activation heteromeric receptor complexes transmembrane, dual-specificity kinases and, thus, define their context-dependent responsiveness ligands. also introduce through which called Smads act as intracellular effectors ligand-induced gene expression show specificity impressive versatility Smad depend cross-talk Last, non-Smad mechanisms, distinct ligand-activated complexes, complement thus contribute cellular responses.

Language: Английский

Citations

622

Extracellular matrix and its therapeutic potential for cancer treatment DOI Creative Commons
Jiacheng Huang,

Lele Zhang,

Dalong Wan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: April 23, 2021

Abstract The extracellular matrix (ECM) is one of the major components tumors that plays multiple crucial roles, including mechanical support, modulation microenvironment, and a source signaling molecules. quantity cross-linking status ECM are factors determining tissue stiffness. During tumorigenesis, interplay between cancer cells tumor microenvironment (TME) often results in stiffness ECM, leading to aberrant mechanotransduction further malignant transformation. Therefore, comprehensive understanding dysregulation TME would contribute discovery promising therapeutic targets for treatment. Herein, we summarized knowledge concerning following: (1) constituents their functions both normal conditions; (2) TME; (3) key receptors alteration during carcinogenesis; (4) current strategies targeting

Language: Английский

Citations

562

Signaling pathways and targeted therapy for myocardial infarction DOI Creative Commons
Qing Zhang, Lu Wang, Shiqi Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 10, 2022

Abstract Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and mortality. Whilst there long way to go for discovering ideal treatments, therapeutic strategies committed cardioprotection cardiac repair following ischemia are emerging. Evidence pathological characteristics in MI illustrates cell signaling pathways that participate survival, proliferation, apoptosis, autophagy cardiomyocytes, endothelial cells, fibroblasts, monocytes, stem cells. These include key players inflammation response, e.g., NLRP3/caspase-1 TLR4/MyD88/NF-κB; crucial mediators oxidative stress instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, Sonic hedgehog; controller fibrosis such as TGF-β/SMADs Wnt/β-catenin; main regulator angiogenesis, PI3K/Akt, MAPK, JAK/STAT, hedgehog, etc. Since play an important role administering process MI, aiming at targeting these aberrant improving manifestations indispensable promising. Hence, drug therapy, gene protein exosome therapy have been emerging known novel therapies. In this review, we summarize by regulating associated pathways, which contribute inhibiting cardiomyocytes death, attenuating inflammation, enhancing so re-functionalize damaged hearts.

Language: Английский

Citations

499

Endothelial to Mesenchymal Transition in Cardiovascular Disease DOI Creative Commons
Jason C. Kovacic, Stefanie Dimmeler, Richard P. Harvey

et al.

Journal of the American College of Cardiology, Journal Year: 2019, Volume and Issue: 73(2), P. 190 - 209

Published: Jan. 1, 2019

Endothelial to mesenchymal transition (EndMT) is a process whereby an endothelial cell undergoes series of molecular events that lead change in phenotype toward (e.g., myofibroblast, smooth muscle cell). EndMT plays fundamental role during development, and mounting evidence indicates involved adult cardiovascular diseases (CVDs), including atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis. Therefore, the targeting may hold therapeutic promise for treating CVD. However, field faces number challenges, lack precise functional definition, understanding causative pathological CVDs (versus being “bystander-phenomenon”), robust human data corroborating extent causality CVDs. Here, we review this emerging but exciting field, propose framework its systematic advancement at translational levels.

Language: Английский

Citations

476

TGF-β receptors: In and beyond TGF-β signaling DOI Creative Commons
Alexandra Vander Ark,

Jingchen Cao,

Xiaohong Li

et al.

Cellular Signalling, Journal Year: 2018, Volume and Issue: 52, P. 112 - 120

Published: Sept. 7, 2018

Language: Английский

Citations

370

Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update DOI
Meenu Mehta, Daljeet Singh Dhanjal, Keshav Raj Paudel

et al.

Inflammopharmacology, Journal Year: 2020, Volume and Issue: 28(4), P. 795 - 817

Published: March 18, 2020

Language: Английский

Citations

314

TGF-β Signaling in Control of Cardiovascular Function DOI Open Access
Marie‐José Goumans, Peter ten Dijke

Cold Spring Harbor Perspectives in Biology, Journal Year: 2017, Volume and Issue: 10(2), P. a022210 - a022210

Published: March 27, 2017

Marie-José Goumans and Peter ten Dijke Department of Molecular Cell Biology Cancer Genomics Centre Netherlands, Leiden University Medical Center, 2300 RC Leiden, The Netherlands Correspondence: m.j.t.h.goumans{at}lumc.nl

Language: Английский

Citations

302