Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers

Kim, S.J.; Nakayama, Satoshi; Shimazu, Kenzo; Tamaki, Yasuhiro; Akazawa, Kenji; Tsukamoto, Fumine; Torikoshi, Yasuhiro; Matsushima, Tomoko; Shibayama, M.; Ishihara, Hideki; Noguchi, Shinzaburo

doi:10.1093/annonc/mdr340

Cited by 28 publications

(15 citation statements)

References 30 publications

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“…In addition, inhibiting CDK1 expression was a potential therapy for MYC-dependent breast cancer (Kang et al, 2014). CDK1 has also been reported to be associated with retinoic acid receptor gamma in cancer cell response, drug resistance, and recurrence of colorectal and breast cancer (Kim et al, 2012;Zeestraten et al, 2012). These results suggest that higher CDK1 levels could lead to CESC progression and increase the malignancy of CESC.…”

Section: Discussionmentioning

confidence: 94%

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

Meng

Liu

Qiu

et al. 2020

DNA and Cell Biology

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Cervical cancer remains a primary cause of female death in developing countries, but its prognosis can be greatly improved if patients are diagnosed earlier. In the present study, we screened the common differentially expressed genes (DEGs) of cervical squamous cell carcinoma (CESC) from dataset GSE7803, Gene Expression Omnibus, and The Cancer Genome Atlas databases. An integrated bioinformatics analysis was performed based on these DEGs for their enrichment in functions and pathways, interaction network, prognostic signature, and candidate molecular drugs. As a result, 164 (114 upregulated and 47 downregulated) DEGs of CESC were identified for further investigation. We then conducted the gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes Pathway analyses to reveal the underlying functions and pathways of these DEGs. In the protein-protein interaction network, hub module and hub genes were identified. Five genes of significant prognostic value-DSG2, ITM2A, CENPM, RIBC2, and MEIS2-were identified by prognostic signature analysis and used to construct a risk linear model. Further validation and investigation suggested DSG2 might be a key gene in CESC prognosis. We then identified two candidate small molecules (trichostatin A and tanespimycin) against CESC. Further validation and exploration of these hub genes are warranted for future prospect in clinical applications.

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Section: Discussionmentioning

confidence: 94%

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

Meng

Liu

Qiu

et al. 2020

DNA and Cell Biology

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“…Hence, the activation status of S-phase regulators may be useful as selection criteria for Wee1 inhibitor eligible patients. Previously, the activation status of CDKs was implemented to predict chemotherapeutic responses in breast cancers (49). In these studies, a profiling-risk score based on Cdk1 and Cdk2 showed that high CDK activity was associated with high pathological complete response rates.…”

Section: Discussionmentioning

confidence: 99%

A haploid genetic screen identifies the G₁/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

Heijink

Blomen

Bisteau

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G 1 /S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G 2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability.cell cycle | checkpoint | AZD-1775 | MK-1775 | polyploidy

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“…Previous study showed that inhibiting the expression of CDK1 is a potential therapy for MYC-dependent breast cancer [9]. The level of CDK1 correlation with treatment resistance and cancer recurrence in patients with colorectal cancer and breast cancer is elevated, and CDK1 also links to RARγ in treatment response of cancer cells [10,11]. In ovarian cancer, it is also shown that CDK1 is essential for sulforaphane-induced G2/M phase arrest [12].…”

Section: Introductionmentioning

confidence: 99%

The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer

Huang

Wang

et al. 2015

Tumor Biol.

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Overexpression of cyclin-dependent kinase 1 (CDK1) has been noted to correlation with several human cancers. However, the effects of CDK1 on ovarian cancer development remain unclear. The aim of this study was to examine the effect of CDK1 and related mechanism in the proliferation and resistance to chemotherapeutic drugs of epithelial ovarian cancer (EOC). Immunohistochemical analysis was performed in 119 human ovarian cancer samples, and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for CDK1 in EOC samples and cell lines to evaluate their protein levels and molecular interaction. Kaplan-Meier survival analysis showed that strong expression of CDK1 exhibited a significant correlation with poor prognosis in human EOC (P = 0.02). Meanwhile, we found that knockdown CDK1 by shCDK1 promoted the apoptosis rate and increased the sensitivity to chemotherapy drugs. Thus, CDK1 might serve as a prognostic marker, and it might be of great value for experimental therapies in EOC.

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Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers

Cited by 28 publications

References 30 publications

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

A haploid genetic screen identifies the G₁/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer

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Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers

Cited by 28 publications

References 30 publications

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer

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A haploid genetic screen identifies the G₁/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity