Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update DOI

Tizhi Wu,

Zhen Qin, Yucheng Tian

et al.

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(22), P. 13228 - 13257

Published: Aug. 31, 2020

Cyclin-dependent kinase 9 (CDK9), which regulates transcriptional elongation, is an attractive therapeutic target for many cancers, especially cancers driven by dysregulation. In particular, CDK9 promotes RNA polymerase II pause/release, a rate-limiting step in normal regulation that frequently dysregulated cancers. Emerging evidence indicates selective inhibition or degradation may provide benefit against certain Indeed, the development of modulators (inhibitors and degraders) has attracted great attention, with several molecules currently under clinical development. This review provides overview recent advances general, special emphasis on compounds evaluation new emerging strategies, such as proteolysis targeting chimeras (PROTACs).

Language: Английский

Regulating tumor suppressor genes: post-translational modifications DOI Creative Commons
Ling Chen, Shuang Liu, Yongguang Tao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: June 10, 2020

Abstract Tumor suppressor genes cooperate with each other in tumors. Three important tumor proteins, retinoblastoma (Rb), p53, phosphatase, and tensin homolog deleted on chromosome ten (PTEN) are functionally associated they regulated by post-translational modification (PTMs) as well. PTMs include phosphorylation, SUMOylation, acetylation, novel modifications becoming growing appreciated. Because most of reversible, normal cells use them a switch to control the state being resting or proliferating, also involve cell survival cycle, which may lead abnormal proliferation tumorigenesis. Although lot studies focus importance kind PTM, further discoveries shows that (TSGs) form complex “network” interaction modification. Recently, there several promising strategies for TSGs change more frequently than carcinogenic cancers. We here review necessity, characteristics, mechanisms Rb, PTEN, its influence precise selective function. discuss current antitumoral therapies p53 PTEN predictive, prognostic, therapeutic target cancer.

Language: Английский

Citations

336

Advances in targeting ‘undruggable’ transcription factors with small molecules DOI
Matthew J. Henley, Angela N. Koehler

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(9), P. 669 - 688

Published: May 18, 2021

Language: Английский

Citations

271

Cell cycle on the crossroad of tumorigenesis and cancer therapy DOI Creative Commons
Jing Liu, Yunhua Peng, Wenyi Wei

et al.

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 32(1), P. 30 - 44

Published: July 22, 2021

Language: Английский

Citations

271

Oncolytic viruses for cancer immunotherapy DOI Creative Commons
Otto Hemminki, João M. Santos, Akseli Hemminki

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: June 29, 2020

Abstract In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments general, with a particular focus on adenoviruses. These serve as model to elucidate how versatile are, and they can be used complement other therapies gain optimal patient benefits. Historical reports from over hundred years suggest treatment efficacy safety adenovirus viruses. This is confirmed more contemporary series multiple clinical trials. Yet, while first have already been granted approval several regulatory authorities, room for improvement remains. As good tolerability seen, virus field has now moved increase wide array approaches. Adding different immunomodulatory transgenes one strategy gaining momentum. Immunostimulatory molecules thus produced at tumor reduced systemic side effects. On hand, preclinical work suggests additive or synergistic effects conventional such radiotherapy chemotherapy. addition, newly introduced checkpoint inhibitors drugs could make perfect companions Especially tumors that seem not recognized by immune system made immunogenic Logically, combination being evaluated ongoing Another promising avenue modulating microenvironment allow T cell solid tumors. Oncolytic next remarkable wave immunotherapy.

Language: Английский

Citations

267

Integrating Old and New Paradigms of G1/S Control DOI Creative Commons
Seth M. Rubin, Julien Sage, Jan M. Skotheim

et al.

Molecular Cell, Journal Year: 2020, Volume and Issue: 80(2), P. 183 - 192

Published: Sept. 17, 2020

Language: Английский

Citations

211

Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response DOI
Kevin C. Johnson, Kevin Anderson, Elise T. Courtois

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(10), P. 1456 - 1468

Published: Sept. 30, 2021

Language: Английский

Citations

189

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

179

Cyclin D-CDK4/6 functions in cancer DOI
Xueliang Gao, Gustavo Leone, Haizhen Wang

et al.

Advances in cancer research, Journal Year: 2020, Volume and Issue: unknown, P. 147 - 169

Published: Jan. 1, 2020

Language: Английский

Citations

160

A unified model for the G1/S cell cycle transition DOI Creative Commons
Samuel Hume, Grigory L. Dianov, Kristijan Ramadan

et al.

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(22), P. 12483 - 12501

Published: Oct. 14, 2020

Efficient S phase entry is essential for development, tissue repair, and immune defences. However, hyperactive or expedited causes replication stress, DNA damage oncogenesis, highlighting the need strict regulation. Recent paradigm shifts conflicting reports demonstrate requirement a discussion of G1/S transition literature. Here, we review recent studies, propose unified model decision. In this model, competition between mitogen signalling over course mother cell cycle constitutes predominant control mechanism daughter cells. Mitogens have distinct sensing periods, giving rise to three Commitment Points (CP1-3). mitogen-independent in G1 phase, but remains sensitive damage, such as single strand breaks, most frequently-occurring lesions that uniquely threaten replication. To CP1-3, dedicated hubs integrate antagonistic mitogenic signals, regulating stoichiometric cyclin: CDK inhibitor ratio ultrasensitive CDK4/6 CDK2. This combines findings decades study, provides an updated foundation research.

Language: Английский

Citations

150

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

140