1,345 results match your criteria inhibitor cdks


Recent Understanding and Future Directions of Recurrent Corticotroph Tumors.

Front Endocrinol (Lausanne) 2021 26;12:657382. Epub 2021 Apr 26.

Neuroendocrinology Clinic, Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. "Non-functioning" or silent CTs (SCT) and the Crooke's cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Read More

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Senescence-associated secretory phenotype and activation of NF-κB in splenocytes of old mice exposed to irradiation at a young age.

Dev Comp Immunol 2021 May 8:104124. Epub 2021 May 8.

Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. Electronic address:

DNA damage-induced cellular senescence is involved in aging. We reported previously that p53 mice subjected to irradiation at a young age exhibited an increased number of splenic lymphocytes in the S and G2/M phases. However, the detailed nature of splenic disorders in these mice is not fully understood. Read More

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Exploring multi-target inhibitors using approach targeting cell cycle dysregulator-CDK proteins.

J Biomol Struct Dyn 2021 Apr 30:1-15. Epub 2021 Apr 30.

Department of Bioinformatics, Hazara University, Mansehra, Pakistan.

Cyclin-dependent kinases (CDKs) belong to a family of multifunctional enzymes that control cell cycle modifications, transcription, and cell proliferation. Their dysfunctions result in different diseases like cancer making them an important drug target in oncology and beyond. The present study aims at identifying the selective inhibitors for ATP binding site in CDK proteins (CDK1, CDK2, CDK4, and CDK5) following a multi-target drug designing approach. Read More

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Oncogenic and Tumor Suppressive Components of the Cell Cycle in Breast Cancer Progression and Prognosis.

Pharmaceutics 2021 Apr 17;13(4). Epub 2021 Apr 17.

Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.

Cancer, a disease of inappropriate cell proliferation, is strongly interconnected with the cell cycle. All cancers consist of an abnormal accumulation of neoplastic cells, which are propagated toward uncontrolled cell division and proliferation in response to mitogenic signals. Mitogenic stimuli include genetic and epigenetic changes in cell cycle regulatory genes and other genes which regulate the cell cycle. Read More

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Trilaciclib: First Approval.

Authors:
Sohita Dhillon

Drugs 2021 May;81(7):867-874

Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.

Trilaciclib (Cosela™) is a small-molecule, short-acting, inhibitor of cyclin-dependent kinases (CDK) 4 and 6 developed by G1 Therapeutics for its myeloprotection and potential antitumor efficacy and safety benefits in combination with cancer chemotherapy. CDKs govern cell cycle progression, and trilaciclib induces a transient, reversible G1 cell cycle arrest of proliferating haematopoietic stem and progenitor cells in bone marrow, thus protecting them from damage during chemotherapy. In February 2021, trilaciclib received its first approval in the USA to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). Read More

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CDK4/6 inhibitor palbociclib reduces inflammation in lupus-prone mice.

Am J Clin Exp Urol 2021 15;9(1):32-43. Epub 2021 Feb 15.

Southeast Louisiana Veterans Health Care System New Orleans, LA, USA.

Lupus is an autoimmune inflammatory disease that affects multiple organs. Cyclin-dependent kinases (CDKs) have been associated with inflammation. The objective of this study was to explore the effects of palbociclib (a CDK4/6 inhibitor) on inflammation in a lupus-prone MRL-lpr mouse model. Read More

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February 2021

Cyclin-dependent kinase inhibitors (CDKIs) and the DNA damage response: The link between signaling pathways and cancer.

DNA Repair (Amst) 2021 Jun 26;102:103103. Epub 2021 Mar 26.

Department of Clinical Microbiology, Sirjan School of Medical Sciences, Sirjan, Iran. Electronic address:

At the cellular level, DNA repair mechanisms are crucial in maintaining both genomic integrity and stability. DNA damage appears to be a central culprit in tumor onset and progression. Cyclin-dependent kinases (CDKs) and their regulatory partners coordinate the cell cycle progression. Read More

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Peptide-Functionalized Nanoparticles-Encapsulated Cyclin-Dependent Kinases Inhibitor Seliciclib in Transferrin Receptor Overexpressed Cancer Cells.

Nanomaterials (Basel) 2021 Mar 18;11(3). Epub 2021 Mar 18.

School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan.

Seliciclib, a broad cyclin-dependent kinases (CDKs) inhibitor, exerts its potential role in cancer therapy. For taking advantage of overexpressive transferrin receptor (TfR) on most cancer cells, T7 peptide, a TfR targeting ligand, was selected as a targeting ligand to facilitate nanoparticles (NPs) internalization in cancer cells. In this study, poly(d,l-lactide-co-glycolide) (PLGA) was conjugated with maleimide poly(ethylene glycol) amine (Mal-PEG-NH) to form PLGA-PEG-maleimide copolymer. Read More

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Discovery and resistance mechanism of a selective CDK12 degrader.

Nat Chem Biol 2021 Mar 22. Epub 2021 Mar 22.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

Cyclin-dependent kinase 12 (CDK12) is an emerging therapeutic target due to its role in regulating transcription of DNA-damage response (DDR) genes. However, development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13. In the present study, we report the rational design and characterization of a CDK12-specific degrader, BSJ-4-116. Read More

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A novel histone deacetylase inhibitor MPT0L184 dysregulates cell-cycle checkpoints and initiates unscheduled mitotic signaling.

Biomed Pharmacother 2021 Jun 16;138:111485. Epub 2021 Mar 16.

Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; TMU Biomedical Commercialization Center, Taipei Medical University, Taipei, Taiwan. Electronic address:

Aberrant alteration of epigenetic information disturbs chromatin structure and gene function, thereby facilitating cancer development. Several drugs targeting histone deacetylases (HDACs), a group of epigenetic enzymes, have been approved for treating hematologic malignancies in the clinic. However, patients who suffer from solid tumors often respond poorly to these drugs. Read More

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Inhibition of Cyclin-dependent Kinase (CDK) Decreased Survival of NB4 Leukemic Cells: Proposing a p53-Independent Sensitivity of Leukemic Cells to Multi-CDKs Inhibitor AT7519.

Iran J Pharm Res 2020 ;19(3):144-155

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

An unbounded number of events exist beneath the intricacy of each particular hematologic malignancy, prompting the tumor cells into an unrestrained proliferation and invasion. Aberrant expression of cyclin-dependent kinases (CDKs) is one of these events which disrupts the regulation of cell cycle and subsequently, results in cancer progression. In this study, we surveyed the repressive impact of multi-CDK inhibitor AT7519 on a panel of leukemia-derived cell lines. Read More

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January 2020

New Insights into CDK Regulators: Novel Opportunities for Cancer Therapy.

Trends Cell Biol 2021 May 3;31(5):331-344. Epub 2021 Mar 3.

Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC, H3C 3J7, Canada. Electronic address:

Cyclins and their catalytic partners, the cyclin-dependent kinases (CDKs), control the transition between different phases of the cell cycle. CDK/cyclin activity is regulated by CDK inhibitors (CKIs), currently comprising the CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family and the inhibitor of kinase (INK) family. Recent studies have identified a third group of CKIs, called ribosomal protein-inhibiting CDKs (RPICs). Read More

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GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.

Cell Death Dis 2021 Mar 3;12(3):231. Epub 2021 Mar 3.

Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China.

Acute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma-associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Read More

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Structure-based design of highly selective 2,4,5-trisubstituted pyrimidine CDK9 inhibitors as anti-cancer agents.

Eur J Med Chem 2021 Mar 2;214:113244. Epub 2021 Feb 2.

School of Pharmacy and Biodiscovery Institute, University of Nottingham, University Park, Nottingham, NG7 2RD, UK; Drug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5001, Australia. Electronic address:

Cyclin-dependent kinases (CDKs) are a family of Ser/Thr kinases involved in cell cycle and transcriptional regulation. CDK9 regulates transcriptional elongation and this unique property has made it a potential target for several diseases. Due to the conserved ATP binding site, designing selective CDK9 inhibitors has been challenging. Read More

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A novel WEE1 pathway for replication stress responses.

Nat Plants 2021 02 11;7(2):209-218. Epub 2021 Feb 11.

College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.

DNA replication stress poses a severe threat to genome stability and is a hallmark of cancer as well as a target for cancer therapy. It is well known that the evolutionarily conserved protein kinase WEE1 regulates replication stress responses by directly phosphorylating and inhibiting the major cell cycle driver CDKs in many organisms. Here, we report a novel WEE1 pathway. Read More

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February 2021

The expression regulation of Cyclins and CDKs in ovary via miR-9c and miR-263a of Scylla paramamosain.

Comp Biochem Physiol B Biochem Mol Biol 2021 Jun-Jul;254:110567. Epub 2021 Feb 4.

Fujian Engineering Research Center of Aquatic Breeding and Healthy Aquaculture, Fisheries College, Jimei University, Xiamen 361021, China; Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, China. Electronic address:

Scylla paramamosain is an economically important cultured crab species in China. Cyclins and cyclin-dependent kinases (CDKs) play important roles in regulations of cell cycle and ovarian development. MiRNAs can negatively regulate gene expression at the post-transcriptional level through base-complementary pairing with the 3'-untranslated region (3-UTR) of the target gene. Read More

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February 2021

Targeting Aberrant FGFR Signaling to Overcome CDK4/6 Inhibitor Resistance in Breast Cancer.

Cells 2021 Feb 1;10(2). Epub 2021 Feb 1.

Department of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.

Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Therapies targeting molecular pathways altered in BC had significantly enhanced treatment options for BC over the last decades, which ultimately improved the lives of millions of women worldwide. Among various molecular pathways accruing substantial interest for the development of targeted therapies are cyclin-dependent kinases (CDKs)-in particular, the two closely related members CDK4 and CDK6. Read More

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February 2021

Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs.

Acta Pharm Sin B 2021 Jan 23;11(1):30-54. Epub 2020 May 23.

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases (CDKs) is a hallmark of cancer. The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs. In particular, third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition, exhibiting a perfect balance between anticancer efficacy and general toxicity. Read More

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January 2021

Allostery governs Cdk2 activation and differential recognition of CDK inhibitors.

Nat Chem Biol 2021 04 1;17(4):456-464. Epub 2021 Feb 1.

Department of Pharmacology and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.

Cyclin-dependent kinases (CDKs) are the master regulators of the eukaryotic cell cycle. To become activated, CDKs require both regulatory phosphorylation and binding of a cognate cyclin subunit. We studied the activation process of the G1/S kinase Cdk2 in solution and developed a thermodynamic model that describes the allosteric coupling between regulatory phosphorylation, cyclin binding and inhibitor binding. Read More

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A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights.

Molecules 2021 Jan 14;26(2). Epub 2021 Jan 14.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf Province, Saudi Arabia.

Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold () was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound.

Methods: The potential anti-cancerous effect of was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Read More

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January 2021

Cellular and Molecular Mechanisms of R/S-Roscovitine and CDKs Related Inhibition under Both Focal and Global Cerebral Ischemia: A Focus on Neurovascular Unit and Immune Cells.

Cells 2021 Jan 8;10(1). Epub 2021 Jan 8.

Inserm, Université Brest, EFS, UMR 1078, GGB, F-29200 Brest, France.

Ischemic stroke is the second leading cause of death worldwide. Following ischemic stroke, Neurovascular Unit (NVU) inflammation and peripheral leucocytes infiltration are major contributors to the extension of brain lesions. For a long time restricted to neurons, the 10 past years have shown the emergence of an increasing number of studies focusing on the role of Cyclin-Dependent Kinases (CDKs) on the other cells of NVU, as well as on the leucocytes. Read More

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January 2021

CDKN2A (p16INK4A) affects the anti‑tumor effect of CDK inhibitor in somatotroph adenomas.

Int J Mol Med 2021 Feb 2;47(2):500-510. Epub 2020 Dec 2.

Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China.

The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA‑Seq, RT‑PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. Read More

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February 2021

Discovery of selective CDK9 degraders with enhancing antiproliferative activity through PROTAC conversion.

Eur J Med Chem 2021 Feb 10;211:113091. Epub 2020 Dec 10.

State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Cyclin-dependent kinase 9 (CDK9) is an increasingly important potential cancer treatment target. Nowadays, developing selective CDK9 inhibitors has been extremely challenging as its ATP-binding sites are similar with other CDKs. Here, we report that the CDK9 inhibitor BAY-1143572 is converted into a series of proteolysis targeting chimeras (PROTACs) which leads to several compounds inducing the degradation of CDK9 in acute myeloid leukemia cells at a low nanomolar concentration. Read More

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February 2021

Mechanisms of Cd and Cu induced toxicity in human gastric epithelial cells: Oxidative stress, cell cycle arrest and apoptosis.

Sci Total Environ 2021 Feb 23;756:143951. Epub 2020 Nov 23.

Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Cadmium (Cd) and copper (Cu) are widely present in foods. However, their adverse effects on human gastric epithelium are not fully understood. Here, human gastric epithelial cells (SGC-7901) were employed to study the toxicity and associated mechanisms of Cd + Cu co-exposure. Read More

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February 2021

A new linear cyclin docking motif that mediates exclusively S-phase CDK-specific signaling.

EMBO J 2021 01 19;40(2):e105839. Epub 2020 Nov 19.

Institute of Technology, University of Tartu, Tartu, Estonia.

Cyclin-dependent kinases (CDKs), the master regulators of cell division, are activated by different cyclins at different cell cycle stages. In addition to being activators of CDKs, cyclins recognize various linear motifs to target CDK activity to specific proteins. We uncovered a cyclin docking motif, NLxxxL, that contributes to phosphorylation-dependent degradation of the CDK inhibitor Far1 at the G1/S stage in the yeast Saccharomyces cerevisiae. Read More

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January 2021

Discovery of 12O-A Novel Oral Multi-Kinase Inhibitor for the Treatment of Solid Tumor.

Molecules 2020 Nov 9;25(21). Epub 2020 Nov 9.

Department of Medicinal Chemistry, School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.

A novel series of pyrimidine-benzotriazole derivatives have been synthesized and evaluated for their anticancer activity against human solid tumor cell lines. The most promising molecule was identified for its excellent antiproliferative activities, especially against the SiHa cell line with IC value as 0.009 μM. Read More

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November 2020

Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer.

Oncol Rep 2020 Dec 22;44(6):2581-2594. Epub 2020 Oct 22.

School of Life Science, Pharmacy and Chemistry, Kingston University London, Surrey KT1 2EE, UK.

Pancreatic cancer is one of the most aggressive, heterogeneous and fatal type of human cancers for which more effective therapeutic agents are urgently needed. Here, we investigated the sensitivity of a panel of seven human pancreatic cancer cell lines (HPCCLs) to treatment with various tyrosine kinase inhibitors (TKIs), cyclin‑dependent kinase (CDK) inhibitors, an inhibitor of STAT3 stattic, and a cytotoxic agent gemcitabine both as single agents and in combination. The membranous expression of various receptors and the effect of selected agents on cell cycle distribution, cell signaling pathways and migration was determined using flow cytometry, western blot analysis and scratch wound healing assays, respectively. Read More

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December 2020

Dinaciclib, a cyclin-dependent kinase inhibitor, suppresses cholangiocarcinoma growth by targeting CDK2/5/9.

Sci Rep 2020 10 28;10(1):18489. Epub 2020 Oct 28.

California Pacific Medical Center Research Institute, 475 Brannan St, Suite 130, San Francisco, CA, 94107, USA.

Cholangiocarcinoma (CCA) is a highly invasive cancer, diagnosed at an advanced stage, and refractory to surgical intervention and chemotherapy. Cyclin-dependent kinases (CDKs) regulate cell cycle progression and transcriptional processes, and are considered potential therapeutic targets for cancer. Dinaciclib is a small molecule multi-CDK inhibitor targeting CDK 2/5/9. Read More

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October 2020

Investigation of the Effect of 5-Aza-2'-Deoxycytidine on p15INK4, p16INK4, p18INK4, and p19INK4 Genes Expression, Cell Growth Inhibition, and Apoptosis Induction in Hepatocellular Carcinoma PLC/PRF/5 Cell Line.

Adv Biomed Res 2020 31;9:33. Epub 2020 Jul 31.

Student of Research Committee, Jahrom University of Medical Sciences, Jahrom, Fars Province, Iran.

Background: Cyclin-dependent kinases (CDKs) are the key regulators of cell-cycle transitions and characterized by needing a separate subunit, a cyclin, which provides domains essential for enzymatic activity. The activities of cyclin-CDK complexes are controlled by a group of molecules that inhibit CDK activity and CDK inhibitors (CKIs). Cancer often exhibits an aberrant CpG methylation of promoter regions of tumor suppressor genes such as CKIs. Read More

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Cyclin E: a potential treatment target to reverse cancer chemoresistance by regulating the cell cycle.

Am J Transl Res 2020 15;12(9):5170-5187. Epub 2020 Sep 15.

Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.

The cyclin family plays important roles in regulating the proliferative cycle of mammalian cells. Among the members of this family, cyclin E regulates multiple downstream molecules, such as the retinoblastoma susceptibility gene (RB1) and the transcription factor E2F, by interacting with cyclin-dependent kinases (CDKs) and plays an important role in the cell cycle transition from G1 to S phase. Over the years, studies have shown that cyclin E is closely related to the chemotherapy resistance of tumor cells and that its expression in tumor cells is closely related to prognosis. Read More

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September 2020