BRAF mutations in thyroid cancer DOI
Rafael Selbach Scheffel, José Miguel Dora, Ana Luiza Maia

et al.

Current Opinion in Oncology, Journal Year: 2021, Volume and Issue: 34(1), P. 9 - 18

Published: Oct. 11, 2021

Activating mutations in the mitogen-activated protein kinase (MAPK) pathway play an important role papillary (PTC) and anaplastic (ATC) thyroid cancer. The aim of this review is to discuss impact BRAF on clinical features treatment patients with cancer.Despite unfavorable course associated PTCs harboring V600E mutation, its prognostic remains debated. V600E-driven tumors exhibit high Extracellular signal-regulated phosphorylation, leading unregulated cell proliferation inhibition required genes for radioiodine responsiveness mechanism variable BRAF-mutant tumor aggressiveness unclear other pathways are likely co-operate promote cancer progression. Overexpression Notch signaling loss individual switch/ sucrose non-fermentable chromatin-remodeling complexes subunits might be involved. combination inhibitor dabrafenib trametinib has shown remarkable results trials BRAF-mutated ATCs.The outcomes PTC debatable. In ATCs, turn, identify eligible targeted therapy, which now considered two settings: as neoadjuvant unresectable a metastatic or disease.

Language: Английский

Biomolecular Condensates and Cancer DOI Creative Commons
Ann Boija, Isaac A. Klein,

Richard A. Young

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(2), P. 174 - 192

Published: Jan. 9, 2021

Language: Английский

Citations

238
Hepatocellular carcinoma: old friends and new tricks DOI Creative Commons
Eunsun Kim, Patrick Viatour

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(12), P. 1898 - 1907

Published: Dec. 1, 2020

Abstract Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and a leading cause of cancer-related deaths worldwide. Ninety percent HCC cases arise from cirrhosis, during which cells undergo chronic cycles necrosis regeneration. The complex genomic landscape has been extensively investigated to draw correlations between recurrently mutated pathways patient prognosis. However, our limited success with targeted therapy shows that knowing presence somatic mutations alone insufficient for us gauge full spectrum their functional consequences in context tumor evolution. In addition, current molecular classification offers little information on relationship features immunological properties tumors immune microenvironment. This review introduces challenges advancements made surveillance, diagnosis, treatment. We also discuss suite HCC-associated genetic changes describe recent studies provide evidence an evolving model its implications understanding targeting progression.

Language: Английский

Citations

236
Acute BAF perturbation causes immediate changes in chromatin accessibility DOI
Sandra Schick,

Sarah Grosche,

Katharina Eva Kohl

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(3), P. 269 - 278

Published: Feb. 8, 2021

Language: Английский

Citations

142
Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021 DOI Creative Commons
Qing Wu, Wei Qian,

Xiaoli Sun

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Oct. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Language: Английский

Citations

135
Molecular events in neuroendocrine prostate cancer development DOI
Yong Wang, Yu Wang,

Xinpei Ci

et al.

Nature Reviews Urology, Journal Year: 2021, Volume and Issue: 18(10), P. 581 - 596

Published: July 21, 2021

Language: Английский

Citations

122
cBAF complex components and MYC cooperate early in CD8+ T cell fate DOI
Ao Guo,

Hongling Huang,

Zhexin Zhu

et al.

Nature, Journal Year: 2022, Volume and Issue: 607(7917), P. 135 - 141

Published: June 22, 2022

Language: Английский

Citations

117
Transcriptional repression of estrogen receptor alpha by YAP reveals the Hippo pathway as therapeutic target for ER+ breast cancer DOI Creative Commons
Shenghong Ma,

Tracy Tang,

Gary D. Probst

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 25, 2022

Abstract Extensive knowledge has been gained on the transcription network controlled by ERα, however, mechanism underlying ESR1 (encoding ERα) expression is less understood. We recently discovered that Hippo pathway required for proper of . YAP/TAZ are coactivators phosphorylated and inhibited kinase LATS. Here we delineated molecular mechanisms repression pathway. Mechanistically, YAP binds to TEAD increase local chromatin accessibility stimulate nearby genes. Among target genes, Vestigial-Like Protein 3 (VGLL3) competes with binding factor recruits NCOR2/SMRT repressor super-enhancer gene, leading epigenetic alteration transcriptional silencing. developed a potent LATS inhibitor VT02956. Targeting VT02956 represses inhibits growth ER + breast cancer cells as well patient-derived tumour organoids. Moreover, histone deacetylase inhibitors, such Entinostat, induce VGLL3 inhibit cells. Our study suggests unexpected therapeutic targets, especially endocrine-resistant cancers.

Language: Английский

Citations

96
Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential DOI Creative Commons
Xuemeng Xu, Peng Qiu,

Xianjie Jiang

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

Citations

96
Structure of human chromatin-remodelling PBAF complex bound to a nucleosome DOI
Junjie Yuan, Kangjing Chen, Wenbo Zhang

et al.

Nature, Journal Year: 2022, Volume and Issue: 605(7908), P. 166 - 171

Published: April 27, 2022

Language: Английский

Citations

82
Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers DOI Creative Commons

Jennifer Cantley,

Xiaofen Ye, Emma Rousseau

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 10, 2022

The mammalian SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4 is frequently mutated in cancer and inactivation results a cellular dependence on its paralog, SMARCA2, thus making SMARCA2 an attractive synthetic lethal target. However, published data indicates that achieving high degree of selective inhibition likely essential to afford acceptable therapeutic index, realizing this objective challenging due the homology with paralog. Herein we report discovery potent proteolysis-targeting chimera molecule (PROTAC), A947. Selective degradation achieved absence SMARCA2/4 PROTAC binding translates vitro growth vivo efficacy mutant models, compared wild type models. Global ubiquitin mapping proteome profiling reveal no unexpected off-target related A947 treatment. Our study highlights ability transform non-selective SMARCA2/4-binding ligand into efficacious SMARCA2-targeting PROTAC, thereby provides potential new opportunity for patients whose tumors contain mutations.

Language: Английский

Citations

79