Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B DOI Creative Commons
Martina Musella, Andrea Guarracino,

Nicoletta Manduca

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(9), P. 1379 - 1392

Published: Aug. 24, 2022

Cancer stem cells (CSCs) are a subpopulation of cancer endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms acquired resistance increasingly being discovered, but molecular insights into the evolutionary process CSCs limited. Here, we show that type I interferons (IFNs-I) function as hubs during immunogenic chemotherapy, triggering epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring towards stemness immune escape. Accordingly, KDM1B inhibition prevents appearance IFN-I-induced CSCs, both in vitro vivo. Notably, heterogeneous terms multidrug resistance, plasticity, invasiveness immunogenicity. Moreover, breast (BC) patients receiving anthracycline-based positively correlated CSC signatures. Our study identifies IFN-I → axis potent engine cell reprogramming, supporting targeting attractive adjunctive drugs prevent expansion increase long-term benefit therapy.

Language: Английский

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives DOI Creative Commons
Lei Zhong, Yueshan Li, Liang Xiong

et al.

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

Published: May 31, 2021

Abstract Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since first tyrosine kinase inhibitor imatinib was approved enter market by US Food Drug Administration (FDA) 2001, an increasing number of small-molecule been developed for treatment malignancies. By December 2020, 89 antitumor FDA National Medical Products (NMPA) China. Despite great progress, anti-cancer still face many challenges, such as a low response rate drug resistance. To better promote development we conducted comprehensive review according target classification. We present all well important candidates clinical trials each target, discuss current provide insights perspectives research drugs.

Language: Английский

Citations

1143
Metabolic reprogramming and epigenetic modifications on the path to cancer DOI Creative Commons
Linchong Sun, Huafeng Zhang, Ping Gao

et al.

Protein & Cell, Journal Year: 2021, Volume and Issue: 13(12), P. 877 - 919

Published: May 29, 2021

Abstract Metabolic rewiring and epigenetic remodeling, which are closely linked reciprocally regulate each other, among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes a consequence translocation spatial regionalization metabolites. Various metabolic alterations modifications also reportedly drive immune escape impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how reprogramming cells reshapes alterations, particular acetylation methylation histone proteins DNA. We discuss other eminent such as, succinylation, hydroxybutyrylation, lactylation, update current advances metabolism- modification-based therapeutic prospects cancer.

Language: Английский

Citations

432
The language of chromatin modification in human cancers DOI
Shuai Zhao, C. David Allis, Gang Greg Wang

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(7), P. 413 - 430

Published: May 17, 2021

Language: Английский

Citations

293
Histone Deacetylases (HDACs): Evolution, Specificity, Role in Transcriptional Complexes, and Pharmacological Actionability DOI Open Access
Giorgio Milazzo, Daniele Mercatelli, Giulia Di Muzio

et al.

Genes, Journal Year: 2020, Volume and Issue: 11(5), P. 556 - 556

Published: May 15, 2020

Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling gene expression profiles. We provide here a review the recent knowledge accrued zinc-dependent HDAC family across different species, tissues, human pathologies, specifically focusing role of inhibitors as anti-cancer agents. will investigate chemical specificity HDACs discuss their in interactome members chromatin-binding complexes.

Language: Английский

Citations

271
Towards targeting of shared mechanisms of cancer metastasis and therapy resistance DOI
Felix Weiß, Douglas A. Lauffenburger, Peter Friedl

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(3), P. 157 - 173

Published: Jan. 10, 2022

Language: Английский

Citations

193
Current Trends and Future Prospects of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma DOI Open Access
Naoya Kitamura,

Shinya Sento,

Yasumasa Yoshizawa

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 22(1), P. 240 - 240

Published: Dec. 29, 2020

In recent years, advances in drug therapy for head and neck squamous cell carcinoma (HNSCC) have progressed rapidly. addition to cytotoxic anti-cancer agents such as platinum-based (cisplatin carboplatin) taxane-based drugs (docetaxel paclitaxel), epidermal growth factor receptor-tyrosine kinase inhibitors (cetuximab) immune checkpoint anti-programmed death-1 (PD-1) antibodies (nivolumab pembrolizumab) come be used. The importance of is increasing year by year. Therefore, we summarize clinical trials molecular targeted biomarkers HNSCC from previous studies. Here show the current trends future prospects HNSCC.

Language: Английский

Citations

187
Epigenetic modulation of antitumor immunity for improved cancer immunotherapy DOI Creative Commons
Enyong Dai, Zhi Zhu,

Shudipto Wahed

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Dec. 20, 2021

Abstract Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also the activation, differentiation effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics cells impacting cell fate functionality, immunogenicity Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 STING, are regulated via epigenetic or/and cells, checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by tumor-associated stromal Thus, therapeutic strategies implementing modulating drugs expected significantly impact tumor microenvironment (TME) promoting transcriptional metabolic reprogramming local populations, resulting inhibition immunosuppressive (MDSCs Treg) activation anti-tumor T professional antigen presenting (APC), well which can serve non-professional APC. latter instance, agents may coordinately promote inducing de novo expression transcriptionally repressed antigens, increasing neoantigens MHC processing/presentation machinery, activating immunogenic death (ICD). ICD provides a rich source immunogens for cross-priming sensitizing interventional immunotherapy. way, modulators be envisioned effective components combination immunotherapy approaches capable mediating superior efficacy.

Language: Английский

Citations

187
Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges DOI
Shenxin Zeng,

Wenhai Huang,

Xiaoliang Zheng

et al.

European Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 210, P. 112981 - 112981

Published: Oct. 31, 2020

Language: Английский

Citations

166
Big data in basic and translational cancer research DOI Open Access
Peng Jiang, Sanju Sinha, Kenneth Aldape

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(11), P. 625 - 639

Published: Sept. 5, 2022

Language: Английский

Citations

158
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

148