Cdk12 breast cancer

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August undefined, 2024

WebHere we report the development of SR-4835, a highly selective dual inhibitor of CDK12 and CDK13, which disables triple-negative breast cancer (TNBC) cells. Mechanistically, inhibition or loss of CDK12/CDK13 … WebJun 20, 2024 · Furthermore, CDK12 inhibitors reversed de novo and acquired PARPi resistance in BRCA1-mutant breast cancer cells . 4) PARPi-immunotherapy; Jiao et al and her colleagues revealed that PARPi upregulated PD-L1 expression in breast cancer cell lines via inactivating GSK3β, which in return leading to attenuate anticancer immunity.

CDK12 - Wikipedia

WebCyclin-dependent kinase 12 (CDK12) is a gene that encodes a protein that functions in the phosphorylation of the C-terminal of the large subunit of RNA polymerase II, the … WebJul 27, 2024 · Androgen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. didn\u0027t rk

CDK12 drives breast tumor initiation and trastuzumab

WebJun 18, 2024 · CDK12 in Breast Cancer. Increasing evidence shows that CDK12 is closely linked with breast cancer. Interestingly, CDK12 plays distinguishing roles among various subtypes of breast cancer, ... WebAug 30, 2024 · CDK12 kinase inhibition alters oncogenic transcriptional programs and has antitumor activity in both trastuzumab-sensitive and … WebOn chromosome 17, the CDK12 gene is located approximately 200kb proximal to the HER2 (ERBB2) oncogene and is frequently co-amplified in breast tumors[36 37]. In cohorts of … beat tumbado

Syros Presents New Preclinical Data on its CDK12 Inhibitor …

CDK12 drives breast tumor initiation and trastuzumab resistance via …

WebDec 9, 2024 · CDK12 and CDK13 are Ser/Thr protein kinases that regulate transcription and co-transcriptional processes. Genetic silencing of CDK12 is associated with genomic instability in a variety of cancers, including difficult-to-treat breast, ovarian, colorectal, brain and pancreatic cancers, and is synthetic lethal with PARP, MYC or EWS/FLI inhibition. … WebMay 25, 2024 · In breast cancer cells, ALE splicing by CDK12 regulates the expression of DDR activator ATM and DNAJB6 isoforms, which can influence tumorigenesis when … beat tracking datasetWebMar 17, 2024 · In breast cancer cells, regulation by CDK12 modulates ALE splicing of the DNA damage response activator ATM and a DNAJB6 isoform that influences cell invasion and tumorigenesis in xenografts. We found that there is a direct correlation between CDK12 levels, DNAJB6 isoform levels and the migration capacity and invasiveness of breast … beat trap uk drill

"http://www.cancerindex.org/geneweb/CDK12.htm#:~:text=CDK12%20mutations%20have%20been%20reported%20in%20many%20cancers,connects%20somatic%20mutations%20to%20signalling%20in%20breast%20cancer. " - Cdk12 breast cancer

Cdk12 breast cancer

CDK12 promotes tumorigenesis but induces vulnerability …

WebOct 5, 2024 · In 2024, it was found that CDK12 inhibition could enhance the sensitivity of HER2+ breast cancer to HER2-tyrosine kinase inhibitors by inhibiting PI3K/AKT [111, 113]. Inhibition of CDK12 can enhance the efficacy of anti-HER2 tyrosine kinase inhibitor Lapatinib, and dual inhibition of HER2/CDK12 may benefit the prognosis of patients with … WebJul 13, 2024 · For example, ovarian and triple-negative breast cancer cells with the lower expression of CDK12 are more sensitive to the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, and a combination treatment of olaparib and dinaciclib, a nonselective CDK12 inhibitor, synergistically suppressed tumor growth in PDX models.

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WebJan 26, 2024 · In ovarian cancer, CDK12 inhibitor THZ1 markedly downregulates MYC and could be an effective ... Chen Y, Zhou Y, et al. CDK12 promotes breast cancer progression and maintains stemness by ... WebNov 11, 2024 · To address whether CDK12 is an exploitable vulnerability pharmacologically, we developed and tested if small-molecule inhibitors of CDK12 enhanced the anti-breast …

WebMar 22, 2024 · For example, ovarian and triple-negative breast cancer cells with the lower expression of CDK12 are more sensitive to the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, and a combination ... WebApr 8, 2024 · CAMBRIDGE, Mass.--(BUSINESS WIRE)--Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today announced new preclinical data from our CDK12 inhibitor program, demonstrating robust anti-tumor activity of our oral, selective CDK12 inhibitors in models …

WebJun 28, 2024 · More recent studies have implicated CDK12 in regulating mRNA splicing, 3' end processing, pre-replication complex assembly and genomic stability during … WebOct 28, 2024 · Dysfunction in “BRCAness” genes, such as RAD51 and CDK12, can also cause HRD and is an important pathway in the development of ovarian or breast cancer. CDK12 , which promotes transcription in several HR pathway genes, such as BRCA1 , is one of the most frequently mutated genes in ovarian cancer [ 65 , 66 ].

WebJul 10, 2024 · Results. CDK12 genomic alterations were detected in 1.1% of all cases, most frequently in prostate cancer (5.6%), but were also observed at >1% frequency in 11 cancer types. Across multiple cancer types, including prostate, gastric/esophageal, ovarian, breast, and endometrial cancer, the number of FTDs was significantly increased in …

WebJan 4, 2024 · CDK12 promotes tumor initiation, invasion, and metastasis, as well as maintains cancer stem cell self-renewal via activating ErbB–PI3K–AKT or WNT/β-catenin signaling in breast cancer. CDK12 … didn\u0027t rnWebJul 20, 2024 · Although CDK12 has only recently emerged as a potential vulnerability for different cancer types including Ewing sarcoma, triple-negative breast cancer, and hepatocellular carcinoma (Iniguez et al., 2024; Quereda et al., 2024; Wang et al., 2024), we describe here a profound CDK12 dependency in a subgroup of patients with CRC. … beat tunerWebApr 4, 2024 · Abstract. Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family of serine/threonine protein kinases. The CDK12/cyclin K complex regulates the elongation step of RNA transcription by phosphorylating Ser2 on the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II, and … didn\u0027t rjWebOct 4, 2024 · Here, we demonstrate that CDK12 promotes tumor initiation as a novel regulator of cancer stem cells (CSCs) and induces anti-HER2 therapy resistance in … didn\u0027t rmWebJul 10, 2024 · Results. CDK12 genomic alterations were detected in 1.1% of all cases, most frequently in prostate cancer (5.6%), but were also observed at >1% frequency in 11 … didn\u0027t ruWebGene Location [ 1] 17q12. Pathway. Cell cycle control. Gene. CDK12. CDK12 Mutation is present in 1.81% of AACR GENIE cases, with lung adenocarcinoma, prostate … didn\u0027t rzWebMar 3, 2024 · Another oncogenic property of overexpressed CDK12 leads to the downregulation of the DNAJB6-L protein (via ALE splicing of its mRNA), which promotes the cell migration and invasiveness of HER2-positive breast cancer cells . The CDK12-specific focal tandem duplications with a high number of duplications and fusions can lead to the … didn\u0027t rs