• Further confirming these findings, recent research indicates that inhibition of CDK7 may be an effective therapy for HER2-positive breast cancers, even overcoming therapeutic resistance. (wikipedia.org)
  • 5. Inhibition of cyclin-dependent kinase 7 suppresses human hepatocellular carcinoma by inducing apoptosis. (nih.gov)
  • 12. Wee-1 Kinase Inhibition Sensitizes High-Risk HPV+ HNSCC to Apoptosis Accompanied by Downregulation of MCl-1 and XIAP Antiapoptotic Proteins. (nih.gov)
  • 15. Nanomaterial-Facilitated Cyclin-Dependent Kinase 7 Inhibition Suppresses Gallbladder Cancer Progression via Targeting Transcriptional Addiction. (nih.gov)
  • Overexpression of miR-106b-5p avoided JQ1-induced p21 appearance and BRD4 inhibition-associated mobile senescence, whereas miR-106b-5p inhibitor up-regulated p21 and induced mobile senescence. (pkc-inhibitor.com)
  • Finally, we confirmed that inhibition of E2F suppressed the binding of BRD4 towards the promoter of miR-106b-5p and inhibited its transcription, resulting in the elevated p21 amounts and mobile senescence in gastric cancers cells. (pkc-inhibitor.com)
  • To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). (cancerindex.org)
  • 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)
  • Our outcomes reveal a book mechanism where BRD4 regulates cancers cell proliferation by modulating the mobile senescence through E2F/miR-106b-5p/p21 axis and offer brand-new insights into using Wager inhibitors as potential anticancer medications. (pkc-inhibitor.com)
  • Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. (blogspot.com)
  • Dacetuzumab specifically binds to and inhibits the CD40 receptor, thereby inducing apoptosis and inhibiting cellular proliferation via antibody-dependent cellular cytotoxicity (ADCC) in cells that overexpress this receptor. (blogspot.com)
  • Also, gene expression signatures of phenoxbenzamine were consistent with several agents in each case that were known to suppress tumor proliferation, notably, protein kinase C inhibitors, Heat Shock Protein inhibitors, epidermal growth factor receptor inhibitors, and glycogen synthase kinase inhibitors. (fortuneonline.org)
  • 1. Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation. (nih.gov)
  • 2. Transcriptional CDK Inhibitors CYC065 and THZ1 Induce Apoptosis in Glioma Stem Cells Derived from Recurrent GBM. (nih.gov)
  • 4. CDK7 inhibitor THZ1 inhibits MCL1 synthesis and drives cholangiocarcinoma apoptosis in combination with BCL2/BCL-XL inhibitor ABT-263. (nih.gov)
  • Inhibitors of histone deacetylases (HDAC) inhibit malignant cell growth and induce apoptosis through unknown mechanisms. (aacrjournals.org)
  • Here, we report that the expression status of adenomatous polyposis coli (APC) protein determines the relative sensitivity of colon cancer cells to HDAC inhibitor-induced apoptosis. (aacrjournals.org)
  • HCA-7 cells (expressing wild-type β-catenin and APC proteins) are more sensitive to apoptosis induced by HDAC inhibitors valproic acid (VPA) and suberoylanilide hydroxamic acid than SW620 or HT-29 cells (both expressing mutant APC). (aacrjournals.org)
  • These results suggest that APC is a critical determinant of HDAC inhibitor-induced apoptosis in colon cancer cells and survivin is a potential target to enhance apoptotic response to HDAC inhibitors. (aacrjournals.org)
  • Inhibitors of HDAC induce differentiation, growth arrest, and apoptosis in cancer cells, whereas they are relatively nontoxic to normal cells ( 2, 4, 5 ). (aacrjournals.org)
  • The mechanism of apoptosis induced by HDAC inhibitors has not been clearly defined, although it has been recently reported that activation of death receptor pathway ( 6, 7 ), up-regulation of proapoptotic proteins Bmf and Bad ( 8, 9 ), down-regulation of antiapoptotic protein Bcl-2 ( 10 ), and activation of Ku70-inhibited Bax ( 11 ) might be involved in certain types of cancers. (aacrjournals.org)
  • Induction of apoptosis via reactivation of p53 (e.g., by inhibitors of HDAC or MDM2) and targeting of its downstream pathways (i.e. (springermedizin.de)
  • We previously found that TBK1, a kinase that is normally involved in immune cell signaling, prevents apoptosis in cancer cells driven by oncogenic KRAS. (dana-farber.org)
  • Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. (wikipedia.org)
  • Cells from breast cancer tumors were found to have elevated levels of CDK7 and Cyclin H when compared to normal breast cells. (wikipedia.org)
  • Together, these findings indicate that CDK7 therapy might make sense for some breast cancer patients. (wikipedia.org)
  • In 2017 CT7001, an oral CDK7 inhibitor, started a phase 1 clinical trial. (wikipedia.org)
  • THZ1 is an inhibitor for CDK7 that selectively forms a covalent bond with the CDK7-cycH-MAT1 complex. (wikipedia.org)
  • 8. THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors. (nih.gov)
  • 16. THZ1 reveals CDK7-dependent transcriptional addictions in pancreatic cancer. (nih.gov)
  • The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. (nih.gov)
  • This shows that upon launch through the contact-arrested condition, a temporal purchase for the reactivation of inactive p27-cyclin D-cdk4 complexes must can be found: p27 should be Y phosphorylated 1st, straight permitting cyclin H-cdk7 phosphorylation of residue T172 as well as the consequent repair of kinase activity. (azd1152.com)
  • 7. CDK inhibitors upregulate BH3-only proteins to sensitize human myeloma cells to BH3 mimetic therapies. (nih.gov)
  • We established and validated proof-of-concept cell-based assays in a 96-well format using PROTACS for three therapeutic targets BET family proteins, kinases, and KRAS. (pharmaceuticalintelligence.com)
  • Protein ubiquitination is a posttranslational modification that involves the covalent tethering of a small 76 amino acid protein called ubiquitin to target proteins ( Hershko and Ciechanover, 1998 ). (frontiersin.org)
  • Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. (lookformedical.com)
  • Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. (mdpi.com)
  • In vivo evaluation of the bystander effect in mouse models demonstrated that for effective therapy, at least 1% of tumor cells need to be delivered with TK-NTR-encoding MCs. (regenerativemedicine.net)
  • Fms-like tyrosine kinase 3 (FLT3) is a cytokine receptor which belongs in the receptor tyrosine kinase class III. (nih.gov)
  • The advent of HER2-targeted drugs, including monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) and antibody-drug conjugates, has yielded improved prognosis for patients. (biomedcentral.com)
  • HER1 and HER4 have a receptor-dependent tyrosine-kinase domain. (biomedcentral.com)
  • HER2 contains a receptor-independent tyrosine-kinase domain. (biomedcentral.com)
  • HER3 lacks a tyrosine-kinase domain [ 7 ]. (biomedcentral.com)
  • the intracellular region was linked to the single-pass, hydrophobic transmembrane domain, comprising of tyrosine-kinase domain and a tail region that contains several sites of tyrosine phosphorylation. (biomedcentral.com)
  • While RCC are refractory to standard therapies and only showed an approximately 15 - 20% response rate to cytokine treatment, targeted therapies using tyrosine kinase inhibitors (TKI) have shown promising results in advanced RCC, but their clinical efficacy is limited due to the development of resistances to these drugs. (oncotarget.com)
  • B-raf belongs to the the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. (blogspot.com)
  • Several HDAC inhibitors are in clinical trials as anticancer agents ( 12 ). (aacrjournals.org)
  • Valproic acid (VPA) is a standard treatment for a variety of forms of epilepsy and has been shown recently to inhibit HDAC at therapeutic concentrations ( 13 - 15 ). (aacrjournals.org)
  • Suberoylanilide hydroxamic acid (SAHA) is a promising HDAC inhibitor and has shown antitumor activity in solid and hematologic tumors in clinical trials ( 20, 21 ). (aacrjournals.org)
  • Gene expression signatures for PBZ on the CMap platform showed appreciable similarity to classical histone deacetylase (HDAC) inhibitors. (fortuneonline.org)
  • 10. Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer. (nih.gov)
  • Furthermore, specific inhibitors targeting SEs assembly and activation have offered potential targets for treating various tumors including hematological malignancies. (biomedcentral.com)
  • My interest as a medical oncologist and cancer biologist is to identify novel targets for cancer therapy. (dana-farber.org)
  • An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. (blogspot.com)
  • The growth suppressor p53 has been shown to interact with cyclin H both in vitro and in vivo. (wikipedia.org)
  • SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. (cancerindex.org)
  • CD19-directed chimeric antigen receptor (CAR) T cell (CAR-T) therapy with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) are approved for the treatment of relapsed or refractory large B cell lymphoma (LBCL), including de novo diffuse LBCL (DLBCL), primary mediastinal B cell lymphoma (PMBCL), and transformed follicular lymphoma (tFL). (bvsalud.org)
  • Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has recently been added to the armamentarium in the battle against B-cell acute lymphoblastic leukemia (B-ALL). (bvsalud.org)
  • After binding to the EGF receptor, the agent is internalized by the cell, where the diphtheria toxin moiety exerts its cytotoxic effect, inhibiting protein synthesis through ADP-ribosylation of elongation factor 2. (blogspot.com)
  • Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. (dana-farber.org)
  • Furthermore, the neutralizing antibodies selectively inhibit biologically lively TGF Bs, while the receptor kinase inhibitors also shut off the basal Smad phosphory lation that's seen inside the absence of exogenously extra TGF B, so identified as endogenous signalling. (plcsignaling.com)
  • Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. (lookformedical.com)
  • ATR is a potential target for anticancer therapeutics to induce cancer cell death by inhibiting cell cycle arrest pathways in response to chemotherapeutics. (nih.gov)
  • The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (wikipedia.org)
  • By changing the adjustments on histones and DNA, the epigenetic regulators alter the non-covalent connections within and between nucleosomes, resulting in altered chromatin buildings and gene appearance1. (pkc-inhibitor.com)
  • Positional cloning efforts revealed that this locus contains the SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B, member 1 (SMARCB1) gene, also known as human sucrose non-fermenting gene number 5 (hSNF5), integrase interactor 1 (INI1), or 47-Kd Brg1/Bam-associated factor (BAF47). (medscape.com)
  • Searches in CLUE also confirmed the earlier observations of strong similarities between gene expression signatures of phenoxybenzamine and several histone deacetylase inhibitors. (fortuneonline.org)
  • These results suggest that MC delivery via microvesicles can mediate gene transfer to an extent that enables effective prodrug conversion and tumor cell death such that it comprises a promising approach to cancer therapy. (regenerativemedicine.net)
  • Based on molecular docking results, Ligands-3, 5, 14, and 16 were screened among 17 different Pyrrolone-fused benzosuberene compounds as potent and specific inhibitors without any cross-reactivity against different CDK isoforms. (wikipedia.org)
  • Thus, TSN is an attractive target for anti-cancer therapy and a potent tumor marker. (nature.com)
  • these effects on histones have a "therapeutic" value in the application of oncolytic cancer therapy that is herpes-based [5-7]. (fortuneonline.org)
  • Therefore, a suitable therapeutic strategy might be the combination of anti-angiogenic and immune-based treatment as first-line therapy this disease [ 1 ]. (oncotarget.com)
  • Specifically, I have focused on lung cancer clinically with a particular interest in targeting KRAS mutations, which have remained refractory to current therapies. (dana-farber.org)
  • Recently, we discovered that a kinase inhibitor, momelotinib, inhibits TBK1 and JAK signaling and has activity in mouse models of Kras-driven lung cancer. (dana-farber.org)
  • Based on these findings, we have opened a trial together with Gilead Sciences combining momelotinib with the MEK inhibitor trametinib in treatment refractory KRAS mutant lung cancer. (dana-farber.org)
  • My overall goal is to continue this effort clinically and in the lab to refine combination therapy for KRAS-driven lung cancer and improve outcomes for this challenging disease. (dana-farber.org)
  • Cotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer. (dana-farber.org)
  • 14. The mTORC1/2 Inhibitor AZD8055 Strengthens the Efficiency of the MEK Inhibitor Trametinib to Reduce the Mcl-1/[Bim and Puma] ratio and to Sensitize Ovarian Carcinoma Cells to ABT-737. (nih.gov)
  • Our case series supports the use of CD19 CAR-T therapy in relapsed/refractory tCLL/SLL and tMZL. (bvsalud.org)
  • The recent approvals of four CD19-or CD22-targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL) have transformed the treatment of relapsed/refractory (r/r) disease. (bvsalud.org)
  • This single-center retrospective study included all patients with tCLL/SLL, tMZL, tFL, and DLBCL/PMBCL treated with CAR-T therapy outside of a clinical trial setting from November 2017 to May 2021 at Moffitt Cancer Center, Tampa, Florida. (bvsalud.org)
  • BCL2 family antagonists, CDK inhibitors) are promising new approaches. (springermedizin.de)
  • THZ1 was tested on HER2-positive breast cancer cells and exhibited high potency for the cells regardless of their sensitivity to HER2 inhibitors. (wikipedia.org)
  • Of note, HER2 harbors no ligand-binding cleft and HER3 has defective intracellular kinase domain. (biomedcentral.com)
  • The standard therapies for ALL and AML are still suboptimal for many patients, especially pediatric. (nih.gov)
  • Medications concentrating on epigenetic regulators possess emerged as book therapies in cancers treatment. (pkc-inhibitor.com)
  • It functions as a microtubule-stabilizing compound and inhibits mitosis of cancer cells, thereby providing a protective role in the treatment of cancers. (ijpsr.com)
  • It was found that treatment of 250 nM THZ1 was sufficient to inhibit global transcription and that cancer cell lines were sensitive to much lower concentrations, opening up further research into the efficacy of using THZ1 as a component of cancer therapy, as described above. (wikipedia.org)
  • TSN was initially discovered as a transcriptional co-activator interacting with Epstein-Barr nuclear antigen 2 (EBNA2) and promoting EBNA2-dependent transcription. (nature.com)
  • CDK12 and CDK13 could also be inhibited using THZ1 (but at higher concentrations) because they have similar structures in the region surrounding C312. (wikipedia.org)
  • Identification of genetic variations that affect activation and metabolism may permit the development of individualized therapy that optimize effectiveness and minimize toxicity. (basicmedicalkey.com)
  • Template-assisted covalent modification of DCAF16 underlies activity of BRD4 molecular glue degraders. (harvard.edu)
  • Prospective dose modification of some chemotherapy and targeted therapies are essential in patients with impaired organ function to reduce the risk of severe adverse events. (basicmedicalkey.com)
  • Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [ 33 P]ATP. (guidetopharmacology.org)
  • Preclinical models for development of immune-oncology therapies. (dana-farber.org)
  • Our work provides several encouraging preclinical therapies that may ameliorate this problem. (orentreich.org)
  • After the primary tumor is surgically removed, chemotherapy and radiation are indicated as adjuvant therapy. (medscape.com)
  • Patients who present with aggressive forms of NHL, or whose disease converts to an aggressive form, may achieve complete remission with combination chemotherapy regimens, with or without aggressive high-dose consolidation therapy with marrow or stem cell support. (medscape.com)
  • The knockdown of ERp57 significantly enhanced the apoptotic response to anticancer treatment in HCT116 colon cancer cells via a p53-dependent mechanism. (oncotarget.com)
  • CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary. (cancerindex.org)
  • A promising target is cyclin-dependent kinase 5 (CDK5), the hyperactivity of which has been shown to have a role in cancer progression. (nih.gov)
  • Moreover, a few of these chemical substances, this kind of as LY2109761, target the two the TBR I and kinases. (plcsignaling.com)
  • They assemble into hexameric ring complexes that function in the energy-dependent remodeling of macromolecules. (nih.gov)
  • An orally available mesylate salt form of the etexilate prodrug of dabigatran, a benzimidazole and direct thrombin inhibitor with anticoagulant activity. (blogspot.com)
  • Dabigatran reversibly binds to and inhibits the activity of thrombin, a serine protease that converts fibrinogen into fibrin. (blogspot.com)
  • Implementations of immune-checkpoint blockades or CAR-T cell therapy are at the stage of pre-clinical assessments of activity and feasibility. (springermedizin.de)
  • Adjuvant therapy is systemic therapy that is administered to treat any existing micrometastases remaining after surgical excision of localized disease. (basicmedicalkey.com)
  • Because adjuvant therapy is given to patients with no remaining clinical evidence of cancer, the benefit of the treatment cannot be proven for an individual patient but only for patient populations. (basicmedicalkey.com)
  • The effectiveness of adjuvant therapy is measured by the relative and absolute reduction in the risk of recurrence. (basicmedicalkey.com)
  • Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy. (harvard.edu)
  • On the flip side, chemical compounds have even more favorable selleck FAK Inhibitor pharmacological properties compared to the neutraliz ing antibodies. (plcsignaling.com)
  • In an effort to verify that induction of those genes screening compounds was TP dependent and not just a obtaining associated with the specific cell lines picked for your microarray evaluation, we selected representative genes and we analyzed their expression by RT qPCR following drug remedy in WT and TP? (micrornaarray.com)
  • 9. Up-regulation of pro-apoptotic protein Bim and down-regulation of anti-apoptotic protein Mcl-1 cooperatively mediate enhanced tumor cell death induced by the combination of ERK kinase (MEK) inhibitor and microtubule inhibitor. (nih.gov)
  • In this review, we discuss the trials that led to US Food and Drug Administration approval of CAR T-cell therapies in patients with B-ALL. (bvsalud.org)
  • We evaluate the evolving role of allogeneic hematopoietic stem cell transplant in the CAR T-cell era and discuss lessons learned from the first steps with CAR T-cell therapy in ALL. (bvsalud.org)
  • Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is essential for regulating DNA damage checkpoints during the cell cycle. (nih.gov)
  • VHL-dependent alterations in the secretome of renal cell carcinoma: Association with immune cell response? (oncotarget.com)
  • 6. Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance. (nih.gov)
  • These Wager inhibitors (BETis) bind towards the acetylated lysine identification pocket within bromodomains and competitively stop the binding of Wager family members bromodomains to histones or nonhistone protein7,10,11. (pkc-inhibitor.com)
  • TGF b dose dependent response Finally we wondered how numerous ligand concentra tions would influence the cellular response. (plcsignaling.com)