Progression targets cyclin dependent kinase inhibitor. Medical search. Frequent questions

Indeed, only two patients had received prior CDK4/6 inhibitors ( Table 1 ). (medscape.com)
Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. (nih.gov)
Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. (nih.gov)
The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (nih.gov)
CDK4/6 inhibitors are ribociclib , abemaciclib , and palbociclib . (medscape.com)
As standard first-line therapy, everybody gets hormonal therapy and a CDK4/6 inhibitor . (medscape.com)
If a patient comes in and hasn't been on anything or it's been more than 1 year off all therapy, they'll probably receive an AI and a CDK4/6 inhibitor . (medscape.com)
If she is on an AI as adjuvant therapy, she'll receive fulvestrant and a CDK4/6 inhibitor . (medscape.com)
As second-line therapy, if the patient has not had a CDK4/6 inhibitor, then she will get fulvestrant and a CDK4/6 inhibitor . (medscape.com)
If she has had a CDK4/6 inhibitor, then we will test her tumor DNA to see if she has a mutation in PI3KCA . (medscape.com)
Based on survival data, I give a CDK4/6 inhibitor as first-line treatment and for second-line treatment, I give either alpelisib if a patient has PIK3CA mutation or everolimus if not. (medscape.com)
I typically give ribociclib, but it's not clear to me that the three CDK4/6 inhibitors are different. (medscape.com)
The method was applied to the A549 lung cancer cell line, and we identified specific kinases known to have an important role in this type of cancer (TGFBR2, EGFR, PHKG1 and CDK4). (biomedcentral.com)
These data led to the phase III TROPICS-02 trial of 400 patients who experienced disease progression on at least one endocrine therapy, a taxane, and an inhibitor of cyclin-dependent kinases 4/6 (CDK4/6) as well as at least two prior lines of chemotherapy. (ascopost.com)
Cyclin D1 (PRAD-1, bcl-1) is one of the key cell cycle regulators, and functions in association with cdk4 and/or cdk6 by phosphorylating the Rb protein. (thermofisher.com)
Cyclin D1 is a cytoplasmic and nuclear protein that is synthesized during G1 phase and assembles with either cyclin-dependent kinase 4 (CDK4) or CDK6 in response to growth factor stimulation. (thermofisher.com)
Cyclin D1 forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (thermofisher.com)
It has been established that CDK4,6/cyclin D and CDK2/cyclin E/A promote the passage through G1 and S phases, whereas CDK1/cyclin B regulates the transition through the late G2 and mitosis. (sdstate.edu)
Given the involvement of cell-cycle mediators in MPNs, we sought to examine the efficacy of therapy combining ruxolitinib with a CDK4/6 inhibitor (LEE011) and a PIM kinase inhibitor (PIM447). (nih.gov)
Finally, based on recent reports suggesting that low HER2 expression might impact combined endocrine and cyclin-dependent kinase (CDK4/6) inhibition, the investigators performed a sub-analysis of PFS in patients who received first-line treatment with an endocrine agent and a CDK4/6 inhibitor. (medpagetoday.com)
p21, also known as senescent cell-derived inhibitor 1 (Sdi1), wild-type p53-activated fragment 1 (Waf1), Cdk-interacting protein 1 (Cip1), and p53-regulated inhibitor of Cdks (Pic1) inhibits cyclin D-cdk4, cyclin E-cdk3, cyclin A-cdk2, and cyclin A-cdk1. (bdbiosciences.com)
This effect is mediated by the upregulation of a CDK inhibitor p21, which causes the decrease in cyclin D1 and CDK4 protein levels and subsequent reduction of pRb hyperphosphorylation. (molcells.org)
The G 1 phase arrest is associated with the decreased expressions of cyclin D1 and cyclin-dependent kinase 4 (CDK4) and hyperphosphorylated pRb, which is mediated by p21 upregulation. (molcells.org)
Thus, the p21-cyclinD1/CDK4 signaling pathway plays a critical role in ARMS/Kidins220-dependent cell-cycle progression. (molcells.org)
The purpose of this study is to: - Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body. (mycancergenome.org)
Abemaciclib ( CDK4 /6 inhibitors) is an investigational drug that works by interrupting the rapid and uncontrolled growth of cancer cells. (mycancergenome.org)

The pursuit of drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. (sdstate.edu)
In mammalian cells, cell cycle is controlled by the sequential activation of cyclin dependent kinases (CDKs). (sdstate.edu)
Four CDKs (CDKs 1, 2, 4 and 6) and their activating cyclins (A, B, D and E), play key roles in cell cycle progression. (sdstate.edu)
While, expression and activity of cyclins and CDKs are tightly regulated in normal cells, they are often deregulated in cancer cells through frequent overexpression and frequent inactivation. (sdstate.edu)
To address this, numerous biochemical, molecular biological studies were carried out in multiple cancer cell lines along with molecular docking studies to determine the interactions between aspirin/salicylic acid with CDKs and cyclins. (sdstate.edu)
The studies carried out during the course of this dissertation work have established that aspirin, salicylic acid and salicylic acid metabolites and derivatives target all more 4 members of CDK family namely CDKs 1, 2, 4 and 6, the major findings of which are detailed below. (sdstate.edu)
Our studies demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2, B1, D3, CDKs 1, 2, 4 and 6 protein levels in a diverse panel of cancer cell lines. (sdstate.edu)
Cyclins and cyclin-dependent kinases (cdks) are evolutionarily conserved proteins that are essential for cell-cycle control in eukaryotes. (bdbiosciences.com)
These proteins, referred to as inhibitors of Cdk activity (CDkIs) bind to cyclins, cdks or their complexes. (bdbiosciences.com)
Cell proliferation is tightly controlled by the cell-cycle regulatory proteins, primarily by cyclins and cyclin-dependent kinases (CDKs) in the G 1 phase. (molcells.org)
also called CCNB1) cyclin B, a cell cycle inducible protein, prominent in mitosis, which activates cdks. (nih.gov)
also called CCNA1) cyclin A, a cell cycle inducible protein, prominent in S-phase, which activates cdks. (nih.gov)
Cell cycle de-regulation in cancer cells have been associated with overexpression/activity of cyclins, cyclin-dependent kinases (CDKs), cell division cycle 25 (Cdc25) phosphatases and/or decreased expression/mutations of cyclin-dependent kinase inhibitors (CDKIs) (6). (cancerdir.com)
These brakes are regulated by a group of enzymes known as cyclin-dependent kinases (CDKs). (mycancergenome.org)

This cell division process is complex and requires the integration of different pathways such as those involved in cell cycle progression, chromatin modifications, and hormonal signaling. (frontiersin.org)
18. 8-60hIPP5(m)-induced G2/M cell cycle arrest involves activation of ATM/p53/p21(cip1/waf1) pathways and delayed cyclin B1 nuclear translocation. (nih.gov)
12,18,19] The development of specific tyrosine kinase inhibitors that target elements in these pathways has allowed molecularly driven clinical investigation in MCL. (cancernetwork.com)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
To combat this, Dr. Wu's second project elucidates whether TG02, a multi-kinase inhibitor, primarily inhibits cyclin-dependent kinase 9 (CDK9) and can target multiple cancer survival pathways simultaneously. (nih.gov)
A pathway enrichment analysis of the set of kinases identified by the method showed that axon guidance, activation of Rac, and semaphorin interactions pathways are associated to a selective response to therapeutic intervention in this cell line. (biomedcentral.com)
Besides making prediction about the cellular response to drugs, the method identifies critical kinase targets and pathways that are statistically associated to drug sensitivity in a given cell line. (biomedcentral.com)
Activation of JAK-STAT signaling results in dysregulation of key downstream pathways, notably increased expression of cell-cycle mediators including CDC25A and the PIM kinases. (nih.gov)
Currently, the targeted therapies are mainly focused on two lung cancer pathways, the EGFR and the vascular endothelial growth factor (VEGF) pathways. (engineering.org.cn)
Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. (engineering.org.cn)
Intracellular pathways influenced by Bcr-Abl Kinase [24,25,26]. (amsj.org)
A synthesis and simplification of selected pathways (JAK/STAT, Gab2, Lyn kinase, IGF-1 and β-1 integrin) showing the leukaemogenic downstream effects of Bcr-Abl signalling. (amsj.org)
Ethanol exposure activates signaling pathways featuring high-mobility group box 1 and Toll-like receptor 4 (TLR4), resulting in induction of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells, which regulates expression of several cytokine genes involved in innate immunity, and its target genes. (nih.gov)
Together, these changes amplify expression of a large number of genes through kinase signaling pathways that converge on two transcription factors called nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B) and activator protein-1 (AP-1). (nih.gov)

The expressions of matrix metalloproteinases-2/9 (MMP-2/9), cyclin D1/E, cyclin-dependent kinase inhibitor 1B (p27), extracellular regulated protein kinases 1/2 (ERK1/2), and ERK1/2 phosphorylation were examined by western blotting or quantitative reverse transcription PCR. (hindawi.com)
Interestingly, the miR-17∼92a cluster contains miR-17, miR-18a, miR-19a/b, miR-20a, and miR-92a, which are mediated by the extracellular regulated protein kinases 1/2 (ERK1/2)/ELK1 pathway in endothelial cells [ 14 ]. (hindawi.com)
CDK - a family of cyclin-dependent protein kinases. (nih.gov)
The eIF4A1-dependent translatome of MCF7 cells was defined by polysome profiling, and was shown to be highly enriched for several classes of oncogenic genes, including G-protein constituents, cyclins and protein kinases, and for mRNAs with G/C-rich 5′UTRs with potential to form G-quadruplexes and with 3′UTRs containing microRNA target sites. (nature.com)

n p27Kip1 (also called Cdkn1B) is a member of the Cip/Kip family of cell cycle inhibitors which are characterized by their ability to bind and inhibit cyclin dependent kinases (CDK)/cyclin complexes halting cell cycle progression in the G1 phase [1]. (researchdataservice.com)

19. A p21(waf1)-independent pathway for inhibitory phosphorylation of cyclin-dependent kinase p34(cdc2) and concomitant G(2)/M arrest by the chemopreventive flavonoid apigenin. (nih.gov)
Phosphorylation of monomeric human CDK2 by CAK1 is more efficient than phosphorylation of the binary CDK2-cyclin A complex. (nih.gov)
By contrast, phosphorylation of CDK2 has a negligible effect on the affinity for cyclin A. The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-A resolution. (nih.gov)
In addition, cyclin D1 positively regulates protein phosphorylation, mammary gland epithelial cell proliferation, and fat cell differentiation. (thermofisher.com)
D-type cyclin-CDK complexes act to inactivate the growth-suppressive function of the Rb protein through its phosphorylation, and titrate CDK inhibitors such as p21Cip1 and p27Kip1. (thermofisher.com)
Without growth factor-mediated stimulation, Cyclin D1 is unstable, and undergoes ubiquitin-mediated degradation, which is triggered by its phosphorylation. (thermofisher.com)
The phosphorylation of c-Myc has been investigated and previous studies have suggested a functional association between phosphorylation at Thr58/Ser62 by glycogen synthase kinase 3, cyclin-dependent kinase, ERK2 and C-Jun N-terminal Kinase (JNK) in cell proliferation and cell cycle regulation. (idhinhibitor.com)
Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer In Vitro and In Vivo. (nih.gov)

But now, cyclin-dependent kinase (CDK) 4/6 inhibitors, which nearly double progression-free survival, are priced at roughly $50,000 for 6 months. (ajmc.com)
For these patients who progressed on endocrine therapy, there was a significant prolongation of progression-free survival, and more than double the response rate, including an increased rate of complete response. (lilly.com)
Palbociclib in combination with an AI as first-line therapy in the treatment of estrogen receptor-positive (ER+)/HER2- metastatic breast cancer has shown to have a significant improvement in progression-free survival (PFS). (medscape.com)
[ 11 ] Abemaciclib has also shown to have overall survival benefit in combination with fulvestrant for women with disease progression after endocrine therapy. (medscape.com)
I typically use endocrine therapy plus a cyclin-dependent kinase (CDK) 4/6 inhibitor first because of the progression-free survival (PFS) and overall survival advantage. (medscape.com)
An experimental breast cancer combination being developed by Eli Lilly has hit its key goal of extending progression-free survival (PFS) in certain patients with advanced disease. (pharmatimes.com)
2 Median progression-free survival was 5.5 months, and median overall survival was 12 months. (ascopost.com)
Median progression-free survival was 28.8 months with T-DXd versus 6.8 months with T-DM1. (universimed.com)
摘要： The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). (engineering.org.cn)
Also, no significant survival differences were demonstrated between patients with HER2-low and HER2-zero primary tumors in terms of overall survive ( P =.84), progression free survival ( P =.92), or disease-free survival ( P =.62). (medpagetoday.com)
Since the introduction of the tyrosine kinase inhibitor (TKI), imatinib, in 2000, CML survival rates have increased, to the point where life expectancy is equal to that of the general population. (amsj.org)
Before the advent of tyrosine kinase inhibitors (TKIs), 5-year survival rate for patients aged 20-44 was 40%, and less than 20% for patients over 65 years. (amsj.org)
Bcr-Abl has constitutive tyrosine kinase activity, causing modulated gene transcription, proliferation, and enforced survival of myeloid progenitor cells [14]. (amsj.org)
This trial showed a substantial improvement in progression-free survival. (gabapathway.com)
PI3K kinases function as key signal transducers downstream of cell-surface receptors and key regulators of cell survival and metabolism (7). (gabapathway.com)
The relation between CD105 expression status and HCC prognosis was analyzed using microarray data of 244 HCC cases HSP inhibitor and by Kaplan-Meier survival analysis. (mirnadatabase.com)
Although ARMS/Kidins220 is involved in tumor cell survival and contributes to tumor progression, its role in cell proliferation and cell-cycle progression has never been investigated. (molcells.org)
Progression Free Survival (PFS)assessed at 6 months and Overall Survival (OS). (mycancergenome.org)

The intent-to-treat population of 669 patients was randomized to receive abemaciclib or placebo orally twice a day on a continuous dosing schedule, given in combination with fulvestrant at its approved dose and schedule, until disease progression. (lilly.com)
Palbociclib, ribociclib, and abemaciclib are the three CDK 4/6 inhibitors currently approved by the US Food and Drug Administration. (medscape.com)
The Phase III MONARCH 2 trial assessed abemaciclib (LY2835219), a cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor, in combination with fulvestrant (AstraZeneca's Faslodex) in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy. (pharmatimes.com)

Then endocrine therapy plus phosphoinositide 3 kinase (PI3K) inhibitor if the patient has PIK3CA mutation, or poly (ADP-ribose) polymerase (PARP) inhibitor if the patient is germline positive. (medscape.com)
Alpelisib is a PI3K inhibitor. (medscape.com)
Evidence already exists that the composition of membrane PI that is closely linked to phosphatidylinositol 3- kinase (PI3K) signaling pathway, depends on dietary lipids. (nih.gov)
16,17] In addition, BCR ligation activates the prosurvival phosphoinositide-3 kinase (PI3K) pathway via AKT, which itself has been implicated in MCL pathogenesis. (cancernetwork.com)
PI3K inhibitors therefore offer promising new therapeutic options for this disease. (gabapathway.com)
Areas covered : This review discusses the pharmacologic properties, preclinical development, clinical efficacy, and safety profile of alpelisib, a PI3K inhibitor indicated in HR+/HER2- PIK3CA-mutated advanced breast cancer, describing current therapeutic indication and open questions. (gabapathway.com)
Expert opinion : Following results of the SOLAR-1 trial, alpelisib became the first PI3K inhibitor approved by the U.S. Food and Drug Administration, in combination with fulvestrant, for postmenopausal women and men with HR+/HER2- PIK3CA-mutated advanced breast cancer following progression on or after an endocrine-based regimen. (gabapathway.com)
The identification of patients that are likely to benefit the most from PI3K inhibitors is still eagerly sought. (gabapathway.com)
The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a central oncogenic pathway deregulated in cancer. (gabapathway.com)
The PI3K kinase family comprises 8 enzymes organized into 3 classes (I-III) based on sequence homology. (gabapathway.com)

15. A novel oxiranylchromenone derivative, MHY336, induces apoptosis and cell cycle arrest via a p53- and p21-dependent pathway in HCT116 human colon cancer cells. (nih.gov)
It was found that vitexicarpin may block the cell cycle in Growth 2 Phase (G2)/Mitosis (M) phase by inhibiting the expression of Cyclin-Dependent Kinase 1 (CDK1), Cellular Myelocytomatosis Oncogene (c-myc) and survivin, thereby inhibiting the proliferation and promoting the apoptosis of human non-small cell lung cancer cell line (H322) [ 3 ]. (ijpsonline.com)
Spleen tyrosine kinase (SYK) is amplified in some patients with MCL, and its inhibition leads to the arrest of cell proliferation and apoptosis. (cancernetwork.com)
The broad cyclin-dependent kinase (CDK) inhibitor flavopiridol leads to downregulation of cyclin D1 and induces apoptosis of malignant lymphocytes in vitro and in murine lymphoma models. (cancernetwork.com)
Numerous HDAC inhibitors have been studied and several of them have shown to influence growth, apoptosis and invasiveness in cancer cells both in vitro and in vivo . (biomedcentral.com)
Exposure of JAK2-mutant cell lines to the triple combination of ruxolitinib, LEE011, and PIM447 resulted in expected on-target pharmacodynamic effects, as well as increased apoptosis and a decrease in the proportion of cells in S-phase, compared with ruxolitinib. (nih.gov)
c-Myc is commonly activated in a variety of tumor cells and plays an important role in cellular proliferation, differentiation, apoptosis and cell cycle progression. (idhinhibitor.com)
Our data demonstrate that ERp57 is a promising target for anticancer therapy due to synergistic p53-dependent induction of apoptosis and p53-independent inhibition of proliferation. (oncotarget.com)
Therefore, the agent/s that could simultaneously target the deregulated cell cycle, apoptosis resistance mechanisms and AR would be effective in inhibiting PCA cells proliferation. (cancerdir.com)
Here, we assessed the anti-cancer efficacy of a novel water-soluble phenolic polymer namely p-DGA (poly[3-(3, 4 dihydroxyphenyl) glyceric acid]) (Figure 1A) isolated from the roots of the Caucasian species of comfrey (showed that p-DGA treatment affects cell cycle progression and induces apoptosis in -chronic lymphocyte leukemia cells (14). (cancerdir.com)

Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. (lilly.com)
While individuals with IDH-mutant low-grade gliomas often have slower disease progression and respond more favorably to treatment than those with IDH wildtype tumors, almost all cases eventually transform into more aggressive high-grade gliomas that rapidly progress. (nih.gov)
However, patients often lose response to ruxolitinib or suffer disease progression despite therapy with ruxolitinib. (nih.gov)
However, clonal evolution results in frequent acquisition of driver mutations in patients progressing late on therapy with CDKi and ET (5), and disease progression will eventually occur. (gabapathway.com)
fulvestrant in patients with disease progression following endocrine therapy. (nih.gov)

6. USP39, a direct target of microRNA-133a, promotes progression of pancreatic cancer via the AKT pathway. (nih.gov)
11-13] More specifically, evidence that MCL pathogenesis is antigen-dependent[14] and that these tumors exhibit constitutive B-cell receptor (BCR) activation[15] posits the BCR signaling pathway as a rational prospect for drug development. (cancernetwork.com)
Several key components of this pathway have been explored as potential targets in MCL therapy. (cancernetwork.com)

The F box protein S phase kinase-associated protein 2 regulates adipose mass and adipocyte number in vivo. (nih.gov)
Cyclin-dependent kinase inhibitor p27 regulates activity of cyclin/cyclin-dependent kinase complexes responsible for cell cycle progression. (nih.gov)
12. Serine/arginine-rich splicing factor 7 regulates p21-dependent growth arrest in colon cancer cells. (nih.gov)
Introduction: CDKN1B gene, which encodes a cyclin-dependent kinase (Cdk) inhibitor, regulates the progression throughout G1 to S cell cycle progression. (endocrine-abstracts.org)

Our current understanding of MCL biology affords the opportunity to investigate novel, molecularly targeted therapeutic approaches. (cancernetwork.com)
The method will facilitate the design of new kinase inhibitors and the development of therapeutic interventions with combinations of many inhibitors. (biomedcentral.com)
Therefore it is important to identify new therapeutic targets and new molecules capable of providing adequate medical treatment for patients with BC. (endocrine-abstracts.org)
mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. (engineering.org.cn)
Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer. (engineering.org.cn)
Thus, the identification of non-toxic agents that are effective against both androgen-dependent and androgen-independent PCA would be a better and viable therapeutic approach. (cancerdir.com)

Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). (nih.gov)
a protein kinase that inhibits Cdk1. (nih.gov)

Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. (nih.gov)
In addition, specific proteins classified as CDK inhibitors capable of binding to cyclin/CDK complexes to inhibit their enzyme activity also play a significant role in regulating cell cycle. (sdstate.edu)
Cyclins (regulatory subunits) to form complexes that regulate the progression of the cell cycle. (bdbiosciences.com)
p21 has also shown to be a component of active cyclin-cdk complexes, suggesting that p21-containing complexes may shift between active and inactive states through changes in p21 content. (bdbiosciences.com)

1. USP39 mediates p21-dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis. (nih.gov)
7. EVI1 targets ΔNp63 and upregulates the cyclin dependent kinase inhibitor p21 independent of p53 to delay cell cycle progression and cell proliferation in colon cancer cells. (nih.gov)
MCL is characterized by overexpression of cyclin D1, a cell cycle regulator that promotes cellular proliferation. (cancernetwork.com)
Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. (molcells.org)
AD and the ERK1/2 inhibitor U0126 (10 μ mol/L) inhibited VSMC proliferation and reduced the overexpression of miR-17∼92a. (hindawi.com)
MMPs (MMP-2 and MMP-9) are reported to promote the proliferation of VSMCs [ 7 ] and repressed by the tissue inhibitors of metalloproteinases (TIMPs). (hindawi.com)
Constitutive and aberrant tyrosine kinase activity is responsible for pathological cell proliferation in CML [4]. (amsj.org)
However, the role of ARMS/Kidins220 in cell proliferation and cell-cycle progression has never been investigated. (molcells.org)
Similarly multiple cell cycle inhibitors are upregulated in older cells [19] implying that a cocktail of cell cycle inhibitors including p27Kip1 may need to be developed to force proliferation to occur in older quiescent tissues. (researchdataservice.com)

ER beta from the prostate has a high affinity for genistein, a major soy isoflavone, which has several biological effects including a protein tyrosine kinase (PTK) inhibitor, an antioxidant, an inhibitor of angiogenesis, a blocker of topoisomerase II, an arrester of the cell cycle at the G2/M stage as well as acting as a phytoestrogen. (nih.gov)
11] Acting downstream of SYK, Bruton tyrosine kinase (BTK) is a promising target in a variety of B-cell malignancies, including MCL. (cancernetwork.com)
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder caused by BCR-ABL1 igureusion encoding for a tyrosine kinase oncoprotein. (amsj.org)
Imatinib antagonises tyrosine kinase activity by competing with ATP binding to the Bcr-Abl protein, reducing unchecked cell-cycle progression [3]. (amsj.org)
This creates the BCR-ABL1 oncogene on the Ph chromosome encoding for Bcr-Abl tyrosine kinase, or p210BCR/ABL [9-11]. (amsj.org)

Endocrine therapy as first-line treatment is either fulvestrant (if patient has relapse on an aromatase inhibitor [AI]) or an AI. (medscape.com)
The BYLieve trial suggests alpelisib- fulvestrant benefit after progression on CDK 4/6 inhibitors. (gabapathway.com)
IBRANCE tablets are taken orally with or without food in combination with an aromatase inhibitor or fulvestrant. (nih.gov)

The development of targeted therapies, including cyclin-dependent kinase (CDK) 4/6 inhibitors and mammalian target of rapamycin (mTOR) inhibitors, have transformed the treatment of HR+/HER2- metastatic breast cancer. (medscape.com)
If neither, then I just prescribe endocrine therapy or endocrine therapy plus a mammalian target of rapamycin (mTOR) inhibitor. (medscape.com)

This upregulation was correlated with tumor progression. (molvis.org)
These techniques will help uncover the intracellular changes that indicate tumor progression without the need for biopsy or surgery. (nih.gov)
Blood-based proteomic signatures associated with MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression. (nih.gov)
A Blood-based Polyamine Signature Associated With MEN1 Duodenopancreatic Neuroendocrine Tumor Progression. (nih.gov)

In this research, we aimed to resolve contradictory results whether SOX9 plays a positive or negative role in melanoma progression and determine whether SOX9 and its closely related member SOX10 share the same or distinct targets in mediating their functions in melanoma. (biomedcentral.com)
Conversely, opposite phenomenon was observed when SOX9 expression was further elevated to a range of high SOX9 expression levels in metastatic melanoma specimens, and that high levels of SOX9 can restore melanoma progression in the absence of SOX10 both in vitro and in vivo. (biomedcentral.com)

Surprisingly we found that known inhibitors of Sirtuin 2 (Sirt2) a deacetylase mimicked A2CE influence on p27Kip1 transcription implicating Sirt2 deacetylation for the inhibitory aftereffect of A2CE on p27Kip1 transcription inhibition. (researchdataservice.com)

These agents are but the first of an exciting class of therapeutics being evaluated as single agents and in combination with inhibitors of poly (ADP-ribose) polymerase (PARP) and immune checkpoint inhibitors. (ascopost.com)
Sacituzumab govitecan is also being evaluated in the early disease setting and in combination with checkpoint inhibitors and PARP inhibitors. (ascopost.com)

Sacituzumab govitecan is a humanized antibody that targets trophoblast cell-surface antigen-2 (Trop-2). (ascopost.com)

Given the significant improvement in PFS with CDK 4/6 inhibitors in combination with AI, this is the preferred first-line treatment in metastatic ER+/HER2- metastatic breast cancer. (medscape.com)
[ 10 ] The mTOR inhibitor everolimus, in combination with exemestane, has shown to improve PFS in patients with HR+/HER2- metastatic breast cancer who were previously treated with nonsteroidal AI. (medscape.com)
Medscape recently asked breast cancer experts how they sequence targeted agents for HR+, HER2/neu-negative (also known as ErbB-2) metastatic breast cancer. (medscape.com)
I have been using the HER2 inhibitor trastuzumab deruxtecan ( T-DXd ) after first-line chemotherapy - typically capecitabine because it is oral and doesn't make your hair fall out. (medscape.com)

The decrease in cyclin A2 and cyclin B1 levels as well as CDK1 and CDK2 protein levels were associated with a corresponding decrease in the levels of messenger RNAs, suggesting that both aspirin salicylic acid regulate their expression at both transcriptional and post translational levels. (sdstate.edu)
The decrease in cyclin A2 and cyclin B1 protein levels appears to be mediated through 26S proteasomes. (sdstate.edu)

The discovery that ubiquitin chains target proteins to the proteasome, which degrades and recycles proteins, was honored with the Nobel Prize in Chemistry in 2004. (wikipedia.org)
It performs its myriad functions through conjugation to a large range of target proteins. (wikipedia.org)
We hypothesized that aspirin and/or its primary metabolite salicylic acid may target cell cycle regulatory proteins modulating their level as well as functions. (sdstate.edu)
In an urgent need for new drug targets the endoplasmic reticulum (ER) has become a promising candidate since rapidly growing tumor cells upregulate their protein synthesis and therefore depend on efficient folding of nascent secretory proteins in the ER. (oncotarget.com)
Cumulative evidence indicates that cell-cycle progression is mediated by cell-cycle regulatory proteins, such as cyclin D1, cyclin E, and cyclin-dependent kinase inhibitor 1B (p27), which are associated with G0/G1 phase cell-cycle arrest [ 5 ]. (hindawi.com)
Abl and Bcr-Abl are non-receptor tyrosine kinases that travel between the nucleus and the cytoplasm and phosphorylate proteins via SH2 and SH3 domains [16]. (amsj.org)

Cyclin D1 overexpression is the distinguishing aberrancy in MCL. (cancernetwork.com)
Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of tumors and may contribute to tumorigenesis. (thermofisher.com)

We also observed downregulation of Sp1 downstream target genes such as p27, p21, Mcl-1 and survivin. (spandidos-publications.com)
ID1 is a dominant negative inhibitor of transcription that represses cell cycle regulatory genes and is elevated in many tumors. (nih.gov)
As a universal inhibitor of cyclin-dependent kinases and one of the target genes of the tumor suppresser p53, p21Waf1/Cip1 can act as a tumor suppresser through its ability to control cell cycle progression. (ox.ac.uk)
The microRNA (miRNA) profiling was performed, and the target genes of miRNAs were searched from the TargetScan 7.2 database. (hindawi.com)
According to the TargetScan 7.2 database, the target genes of miR-17∼92a act on tissue inhibitors of metalloproteinases (TIMPs)-MMPs, p27/21 cyclins, and peroxisome-proliferator-activated receptor α (PPAR α ) ATP-binding cassette transporter (ABC) A1/G1, which are involved in the process of atherosclerosis. (hindawi.com)

Imatinib resistance in chronic myeloid leukaemia caused by Bcr-Abl kinase domain and non-Bcr-Abl mutations: a comparison and review. (amsj.org)
Literature about resistance has mainly focussed on mutations in the Bcr-Abl kinase domain (KD), which have been well described. (amsj.org)
This review focuses on how KD mutations arise and their mechanisms of resistance and the roles of BCR-ABL1 gene amplification, Erk1, and Lyn kinase in creating resistance outside of the KD. (amsj.org)

A30: Cdc2 (Cdk1), in association with either Cyclin B or Cyclin A, phosphorylates ORC2. (nih.gov)

This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. (nih.gov)

We have prepared phosphorylated cyclin-dependent protein kinase 2 (CDK2) for crystallization using the CDK-activating kinase 1 (CAK1) from Saccharomyces cerevisiae and have grown crystals using microseeding techniques. (nih.gov)
Phosphorylated CDK2 exhibits histone H1 kinase activity corresponding to approximately 0.3% of that observed with the fully activated phosphorylated CDK2-cyclin A complex. (nih.gov)
A29: Cdk2 can bind either Cyclin A or Cyclin E. For details on activation of Cdk2 (PMID: 10436023). (nih.gov)

Between 2017 and 2020, the United States Food and Drug Administration (FDA) approved a variety of drugs for the treatment of HCC, including multikinase inhibitors (regorafenib, lenvatinib, cabozantinib, and ramucirumab), immune checkpoint inhibitors (nivolumab and pembrolizumab), and bevacizumab combined with atezolizumab. (biomedcentral.com)

Administer the recommended dose of an aromatase inhibitor when given with IBRANCE. (nih.gov)
Please refer to the Full Prescribing Information for the aromatase inhibitor being used. (nih.gov)
For men treated with combination IBRANCE plus aromatase inhibitor therapy, consider treatment with an LHRH agonist according to current clinical practice standards. (nih.gov)

Real-World Use of Highly Sensitive Liquid Biopsy Monitoring in Metastatic Breast Cancer Patients Treated with Endocrine Agents after Exposure to Aromatase Inhibitors. (cdc.gov)

An mTOR inhibitor is everolimus , which can be combined with multiple endocrine therapy backbones. (medscape.com)

The ubiquitylation system was initially characterised as an ATP-dependent proteolytic system present in cellular extracts. (wikipedia.org)
These profiled libraries define drug-kinase networks that can predict the effectiveness of untested drugs and elucidate the roles of specific kinases in different cellular systems. (biomedcentral.com)
Predictions of drug effectiveness based on a comprehensive network model of cellular signalling are difficult, due to our partial knowledge of the complex biological processes downstream of the targeted kinases. (biomedcentral.com)
Understanding aspirin-mediated chemopreventive mechanism and pinpointing its direct cellular targets is of high value, if it is to be used as a prophylactic drug. (sdstate.edu)

Possible Molecular Targets for Nutrients Advances in biology have identified several regulatory sites that may serve as potential molecular targets for prostate cancer prevention. (nih.gov)
The regulatory subunit of this kinase is Dbf4/Ddk. (nih.gov)

The ankyrin repeat-rich membrane spanning (ARMS) scaffold protein, also known as kinase D-interacting substrate of 220 kDa (Kidins 220), has been previously identified as a prominent downstream target of neurotrophin and ephrin receptors. (molcells.org)

The following product was used in this experiment: Cyclin D1 Monoclonal Antibody (3D8) from Thermo Fisher Scientific, catalog # MA5-15650, RRID AB_10978307. (thermofisher.com)

Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB). (oncotarget.com)
Therefore, this information may be applied for early cancer detection, classification, novel targeted therapy, and prognosis in NSCLC. (engineering.org.cn)
Recent clinical data have revealed that targeted therapy might be the second-line therapy as an alternative approach. (engineering.org.cn)
Therefore, it is very important to select NSCLC patients with biomarkers to match targeted agents so that we can further identify effectiveness of targeted therapy in the future. (engineering.org.cn)
With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. (engineering.org.cn)
These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. (engineering.org.cn)
Currently, in the absence of visceral crisis, the standard of care for these patients is an endocrine therapy (ET) and cyclin-dependent kinase 4 and 6 inhibitors (CDKi) combination (4). (gabapathway.com)

It has been previously demonstrated that the atypical BC human cell line NCI-H720 is sensitive to everolimus (E), an m-TOR inhibitor, in terms of cell viability reduction, with a G0 cell-cycle arrest and a Cyclin D1 protein reduction. (endocrine-abstracts.org)

Cyclin A:Cdc2 binds ORC and phosphorylates ORC2p in Xenopus (PMID: 10660590). (nih.gov)
P61959.1 MADEKPKEGVKTENNDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQQQTGGVY 1367453_at NP_446195 8.92 hsp90 co-chaperone Cdc37 Cdc37 Rattus norvegicus " Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity. (nih.gov)

Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blots experiments, we compared changes in ETS-1 and ETS-2 expression, their protein levels, and the regulation of some of their target gene expressions at different stages of the ocular tumoral progression in the transgenic mouse model, Tyrp-1-TAg, with those in normal eyes from control mice of the same age. (molvis.org)
Several mechanisms and numerous factors, including an increasing number of noncoding RNAs (ncRNAs), modulate gene transcription at every stage of embryo and fetus development [ 13 ] and pregnancy progression [ 14 ] . (encyclopedia.pub)

Cyclin D1 destabilization participates in G1/S phase arrest. (thermofisher.com)

also called Cdc2) cyclin-dependent protein kinase. (nih.gov)

p21/CIP1 is a Cyclin/Cyclin-dependent kinase (Cdk) inhibitor that blocks progression from G1 to S phase in the cell cycle. (bio-techne.com)
Exogenous transforming growth factor-β 1 increased the gene expression of cyclin-dependent kinase inhibitors, p15 Ink4b , p16 Ink4a , and p21 CIP1 , in endothelial cells. (johnshopkins.edu)

Investigators are encouraged to use in vitro and in vivo studies with various levels of target expression and to address confounding factors that influence the overall physiological response to changes in a given molecular target. (nih.gov)
We have developed the Kinase Inhibitors Elastic Net (KIEN) method, which integrates information contained in drug-kinase networks with in vitro screening. (biomedcentral.com)

May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle. (nih.gov)

The Histone Deacetylase (HDAC) inhibitor Valproic Acid (VA), used for epilepsy and other neuropsychiatric diseases, has been demonstrated a strong antitumoral and cytostatic activity. (biomedcentral.com)

MicroRNAs (miRNAs) are a class of 18-22 nt small noncoding RNAs that bind to the 3′-UTR of the target messenger RNAs (mRNAs) and result in mRNA cleavage and translational repression ( Bartel, 2004 ). (molcells.org)

In humans, the CCND1 gene encoding cyclin D1 is present on chromosome 11. (thermofisher.com)

However, the mechanisms underlying this phenomenon have not been fully clarified.Aim: The aim of our study is to investigate the mechanisms of resistance to mTOR inhibitors in BC cells. (endocrine-abstracts.org)

Cyclin D1 is a putative proto-oncogene overexpressed in a wide variety of human neoplasms including mantle cell lymphomas (MCL). (thermofisher.com)

We also demonstrated upregulation of ETS-1 and ETS-2 target expressions in Tyrp-1-TAg mice when comparing with the same target expressions in control mice. (molvis.org)
Compensatory upregulation of SOX9 expression in SOX10-inhibited melanoma cells reduced growth and migratory capacity, partly due to elevated expression of cyclin-dependent kinase inhibitor p21 and lack of NEDD9 induction. (biomedcentral.com)

Further studies are needed to determine which of these molecular targets is primarily responsible for genistein's antiproliferative effects on prostate cancer cells. (nih.gov)

Indeed, some HDAC inhibitors, alone or in combination with other chemotherapeutic agents, are used in many clinical trials for both hematologic and solid tumors [ 17 ]. (biomedcentral.com)
Valproic acid (VA), a short-chain fatty acid, which has been used for the past two decades in the treatment of epilepsy and other neuropsychiatric diseases, is considered a class I HDAC inhibitor with strong antitumoral activity [ 18 ]. (biomedcentral.com)

Anatomy13

Organisms7

Diseases9

Chemicals and Drugs164

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes48

Disciplines and Occupations1

Information Science3

CDK426

CDKs14

Pathways14

Protein kinases4

Inhibit cyclin-depende1

Phosphorylation8

Survival18

Abemaciclib3

PI3K10

Apoptosis10

Disease progression5

Pathway3

Regulates4

Therapeutic6

Inhibits2

Complexes4

Proliferation9

Tyrosine kinase5

Fulvestrant3

Mammalian2

Tumor progression4

Melanoma progression2

Inhibition1

PARP2

Humanized antibody1

HER24

Decrease in cyclin2

Proteins6

Overexpression2

Genes5

Mutations3

CDK11

Gene encodes1

CDK23

Immune checkpoint inhibitors1

Aromatase inhibitor3

Metastatic breast cancer1

MTOR inhibitor1

Cellular4

Regulatory2

Downstream1

Monoclonal1

Therapy7

Everolimus1

Binds2

Transcription2

Arrest1

Cdc21

Cip12

Vitro2

CCNE11

Histone1

Bind1

Humans1

Resistance1

Oncogene1

Upregulation2

Primarily1

HDAC2