Deciphering the Immunomodulatory Role of Cyclin-Dependent Kinase 4/6 Inhibitors in the Tumor Microenvironment DOI Open Access
Pratibha Pandey, Fahad Khan, Tarun Kumar Upadhyay

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2236 - 2236

Published: Jan. 23, 2023

Cancer is characterized by persistent cell proliferation driven aberrant cycle regulation and stimulation of cyclin-dependent kinases (CDKs). A very intriguing potential approach for the development antitumor medicines suppression CDKs that lead to induction apoptosis arrest. The shift from G0/G1 phase S phase, which active transcription synthesis, depends on cyclin D-CDK4/6 complex. precise balance between anticancer activity general toxicity demonstrated CDK inhibitors, can specifically block CDK4/6 control reducing G1 transition. inhibitors have recently been reported exhibit significant growth inhibition via modulating tumour microenvironment in cancerous cells. One new understanding these serve important functions interaction among cells host immune system addition being cytostatic. Herein, we discuss biological significance cancer therapeutics, as well their impact T other Furthermore, explore integration preclinical findings pharmaceuticals' ability enhance immunity.

Language: Английский

Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling DOI Creative Commons
Zhixiang Wang

Cells, Journal Year: 2021, Volume and Issue: 10(12), P. 3327 - 3327

Published: Nov. 26, 2021

The cell cycle is the series of events that take place in a cell, which drives it to divide and produce two new daughter cells. typical eukaryotes composed following phases: G1, S, G2, M phase. Cell progression mediated by cyclin-dependent kinases (Cdks) their regulatory cyclin subunits. However, driving force growth factor-initiated signaling pathways control activity various Cdk-cyclin complexes. While mechanism underlying role factor G1 phase has been largely revealed due early extensive research, little known regarding function regulating other phases cycle, including In this review, we briefly discuss process through phases, focus on activated factors receptor (mostly tyrosine kinases) phases.

Language: Английский

Citations

150
Molecular and functional imaging in cancer-targeted therapy: current applications and future directions DOI Creative Commons
Jing‐Wen Bai, Si-Qi Qiu, Guo‐Jun Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 27, 2023

Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria Solid Tumor (RECIST) system has been used assess response therapy via changes the size of target lesions measured calipers, conventional anatomically based imaging modalities such computed tomography (CT), magnetic resonance (MRI), other methods. However, RECIST is sometimes inaccurate assessing efficacy targeted because poor correlation between treatment-induced necrosis or shrinkage. This approach might also result delayed identification when does confer a reduction size. Innovative molecular techniques have gained importance dawning era they can visualize, characterize, quantify biological processes at cellular, subcellular, even level anatomical level. review summarizes different pathways, various techniques, developed probes. Moreover, application for evaluating treatment related clinical outcome systematically outlined. In future, more attention should be paid promoting translation sensitivity biocompatible particular, multimodal technologies incorporating advanced artificial intelligence comprehensively accurately cancer-targeted therapy, addition RECIST-based

Language: Английский

Citations

93
Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy DOI Creative Commons

Run Huang,

Huan Chen,

Jiayu Liang

et al.

Journal of Cancer, Journal Year: 2021, Volume and Issue: 12(18), P. 5543 - 5561

Published: Jan. 1, 2021

Reactive oxygen species (ROS) play a dual role in the initiation, development, suppression, and treatment of cancer.Excess ROS can induce nuclear DNA, leading to cancer initiation.Not only that, but also inhibit T cells natural killer promote recruitment M2 polarization macrophages; consequently, escape immune surveillance defense.Furthermore, tumor invasion metastasis by triggering epithelial-mesenchymal transition cells.Interestingly, massive accumulation inhibits growth two ways: (1) blocking cell proliferation suppressing signaling pathway, cycle, biosynthesis nucleotides ATP (2) inducing death via activating endoplasmic reticulum stress-, mitochondrial-, P53-apoptotic pathways ferroptosis pathway.Unfortunately, adapt self-adaption system.This review highlighted bidirectional regulation cancer.The study further discussed application massively accumulated treatment.Of note, self-adaptive ability should be taken into consideration for prevention.

Language: Английский

Citations

101
Cell Cycle Progression and Synchronization: An Overview DOI
Zhixiang Wang

Methods in molecular biology, Journal Year: 2022, Volume and Issue: unknown, P. 3 - 23

Published: Jan. 1, 2022

Language: Английский

Citations

63
CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells DOI Creative Commons
Lei Zhang, Yidong Li, Chaohua Hu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: April 22, 2022

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1/P-gp) is a major cause of cancer chemotherapy failure, but the regulation mechanisms are largely unknown.Based on single gene knockout, we studied CDK6-PI3K axis ABCB1-mediated MDR in human cells. CRISPR/Cas9 technique was performed KB-C2 cells to knockout cdk6 or cdk4 gene. Western blot, RT-PCR and transcriptome analysis were investigate target deletion expression critical signaling factors. The effect deficiency cell apoptosis cycle analyzed using flow cytometry. In vivo studies study sensitivity tumors doxorubicin, tumor growth metastasis.Deficiency led remarkable downregulation ABCB1 reversal MDR. Transcriptomic revealed that CDK6 regulated series factors, among them, PI3K 110α 110β, KRAS MAPK10 downregulated, FOS-promoting autophagy CXCL1-regulating multiple factors upregulated. Notably, 110α/110β in-return downregulated synergizes regulating expression, which strengthened over either 110α/110β. High frequency alternative splicing (AS) premature mRNA induced CDK6, CDK4 level change confirmed alter level, them 10 common skipped exon (SE) events found. experiments demonstrated loss remarkably increased doxorubicin increasing drug accumulation tumors, resulting inhibition metastasis, as well survival nude mice.CDK6-PI3K new reverse reported for first time cancers. Pathways leading proliferation be accompanied deficiency.

Language: Английский

Citations

42
The pathophysiology of the cell cycle in cancer and treatment strategies using various cell cycle checkpoint inhibitors DOI Open Access
Sami G. Almalki

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 251, P. 154854 - 154854

Published: Oct. 4, 2023

Language: Английский

Citations

29
Mechanosensitive Ion Channels and Their Role in Cancer Cells DOI Creative Commons
Julia Karska,

Szymon Kowalski,

Jolanta Saczko

et al.

Membranes, Journal Year: 2023, Volume and Issue: 13(2), P. 167 - 167

Published: Jan. 29, 2023

Mechanical forces are an inherent element in the world around us. The effects of their action can be observed both on macro and molecular levels. They also play a prominent role tissues cells animals due to presence mechanosensitive ion channels (MIChs) such as Piezo TRP families. essential many physiological processes human body. However, pathology has been observed. Recent discoveries have highlighted relationship between these development malignant tumors. Multiple studies shown that MIChs mediate proliferation, migration, invasion various cancer via mechanisms. This could show new potential biomarkers detection prognosis interesting therapeutic targets modern oncology. Our paper is review latest literature Piezo1 families mechanisms carcinogenesis different types cancer.

Language: Английский

Citations

27
Insights into phosphorylation-induced influences on conformations and inhibitor binding of CDK6 through GaMD trajectory-based deep learning DOI
Lu Zhao, Jian Wang, Wanchun Yang

et al.

Physical Chemistry Chemical Physics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

GaMD trajectory-based deep leaning identifies phosphorylation-mediated effects on the function of CDK6.

Language: Английский

Citations

1
CDK4/6 Inhibitors in Melanoma: A Comprehensive Review DOI Creative Commons
Mattia Garutti, Giada Targato, Silvia Buriolla

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1334 - 1334

Published: May 28, 2021

Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed significative improvement prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies completely revolutionized the management of this Nonetheless, not all patients derive benefit or durable from these therapies. To overtake challenges, new clinically active compounds are being tested context clinical trials. CDK4/6 drugs already available practice preliminary evidence showed promising activity also melanoma. Herein we review literature to depict comprehensive landscape about We present molecular genetic background that might justify usage drugs, preclinical evidence, data, most ongoing

Language: Английский

Citations

53
Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology DOI Open Access
Marcin Szymański, Klaudia Bonowicz, Paulina Antosik

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 836 - 836

Published: Feb. 19, 2024

Endometriosis is a gynecological condition where endometrium-like tissue grows outside the uterus, posing challenges in understanding and treatment. This article delves into deep cellular molecular processes underlying endometriosis, with focus on crucial roles played by cyclins cytoskeletal proteins its pathogenesis, particularly context of Epithelial–Mesenchymal Transition (EMT). The investigation begins examining activities cyclins, elucidating their diverse biological such as cell cycle control, proliferation, evasion apoptosis, angiogenesis among ectopic endometrial cells. A comprehensive analysis follows, emphasizing fundamental specific significance to endometriotic features. review sheds light interconnected pathways through which converge, contributing genesis progression endometriosis. Understanding these complexities not only provides insight causes disease but also holds promise for development therapeutic approaches, ushering new era management this devastating disorder.

Language: Английский

Citations

6