Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth <i>In Vitro</i> and <i>In Vivo</i>, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel

Liu, Xianzhe; Gao, Yan; Shen, Jacson K.; Yang, Wen; Choy, Edwin; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng

doi:10.1158/1535-7163.mct-16-0032

Cited by 33 publications

(30 citation statements)

References 44 publications

(65 reference statements)

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“…CDK13 regulates genes required for growth signalling and shows a different gene expression profile after knockdown compared with CDK12. [37] CDK14 is upregulated in ovarian cancer and CDK14 inhibition reduced proliferation, migration and invasion in ovarian cells associated with inhibition of the Wnt singalling pathway. [37]…”

Section: Cdks and Cancermentioning

confidence: 99%

“…[36] Similarly, CDK11 is overexpressed in ovarian cancer and siRNA knockdown inhibits growth, induces apoptosis, and sensitises to paclitaxel. [37] CDK12 is associated with transcriptional regulation, splicing, embryonal development, and DNAdamage response via the homologous repair pathway. CDK12 overexpression has been observed in breast cancer.…”

Section: Cdks and Cancermentioning

confidence: 99%

“…[38] A synthetic lethality screen identified CDK12 as conferring sensitivity to PARP1/2 inhibitor olaparib. [37] Understanding of CDK12 function is not as extensive as for other kinases.…”

Section: Cdks and Cancermentioning

confidence: 99%

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Recent Advances in CDK Inhibitors for Cancer Therapy

et al. 2018

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Inhibition of CDKs is an attractive approach to cancer therapy due to their vital role in cell growth and transcription. Pan-CDK inhibitors have shown some clinical benefit, and trials are ongoing. Selective CDK4 and CDK6 inhibitors have been licensed for the treatment of hormone responsive, RB-positive breast cancer in combination with antihormonal agents. Selective inhibitors of CDKs 5, 7, 8, 9 and 12 have been identified across a range of chemotypes.

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Section: Cdks and Cancermentioning

confidence: 99%

Section: Cdks and Cancermentioning

confidence: 99%

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Recent Advances in CDK Inhibitors for Cancer Therapy

et al. 2018

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“…Aberrant expression and activation of CDK11 has been reported in diverse types of human cancer . Cyclin‐dependent kinase 11 also plays crucial roles in cancer cell growth and proliferation.…”

Section: Biology and Regulation Of Cdks In Hccmentioning

confidence: 99%

“…92,93 Aberrant expression and activation of CDK11 has been reported in diverse types of human cancer. [94][95][96] Cyclindependent kinase 11 also plays crucial roles in cancer cell growth and proliferation. Inhibition of CDK11 has been shown to lead to cancer cell death and apoptosis.…”

Section: Cyclin-dependent Kinase 11mentioning

confidence: 99%

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Shen

Dean²,

et al. 2019

Hepatology Research

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Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.

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Increased mediator complex subunit CDK19 expression associates with aggressive prostate cancer

Becker

Joerg

Hupe

et al. 2019

Intl Journal of Cancer

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The Mediator complex is a transcriptional regulator interacting with transcription factors and RNA‐polymerase‐II. Recently, we identified its subunit CDK19 to be specifically expressed in prostate cancer (PCa) and to be functionally implicated in PCa aggressiveness. Aim of our study was to comprehensively characterize the protein expression of CDK19 and its paralog CDK8 in PCa. We performed immunohistochemistry (IHC) for CDK19/CDK8 on a large cohort including needle biopsies from 202 patients, 799 primary tumor foci of radical prostatectomy specimens from 415 patients, 120 locally advanced tumor foci obtained by palliative transurethral resection, 140 lymph node metastases, 67 distant metastases and 82 benigns. Primary tumors were stained for the proliferation marker Ki67, androgen receptor (AR) and ERG. For 376 patients, clinic–pathologic data were available. Primary endpoint was disease‐recurrence‐free survival (DFS). Nuclear CDK19 and CDK8 expression increases during progression showing the highest intensity in metastatic and castration‐resistant tumors. High CDK19 expression on primary tumors correlates with DFS independently from Gleason grade and PSA. Five‐year‐DFS rates of patients with primary tumors expressing no, moderate and high CDK19 are 73.7, 56.9 and 30.4%, respectively. CDK19 correlates with Gleason grade, T‐stage, Ki67 proliferation‐index, nuclear AR expression and ERG‐status. Therapeutic options for metastatic and castration‐resistant PCa remain limited. In the current study, we confirmed an important role of the Mediator subunit CDK19 in advanced PCa supporting current developments to target CDK19 and its paralog CDK8. Furthermore, CDK19 protein expression has the potential to predict disease recurrence independently from established biomarkers thus contributing to individual management for PCa patients.

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Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel

Cited by 33 publications

References 44 publications

Recent Advances in CDK Inhibitors for Cancer Therapy

Recent Advances in CDK Inhibitors for Cancer Therapy

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Increased mediator complex subunit CDK19 expression associates with aggressive prostate cancer

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