Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib

Kwapisz, Dorota

doi:10.1007/s10549-017-4385-3

Cited by 171 publications

(132 citation statements)

References 59 publications

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“…A previous study reported that dysregulation of the CDK4‐RB pathway is an important contributor to endocrine therapy resistance . To test this, we established the tamoxifen‐resistant MCF7/TR cell line through long‐term culture of ER‐positive MCF7 cells with increasing concentrations of tamoxifen.…”

Section: Resultsmentioning

confidence: 99%

Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models

Long

et al. 2019

Cancer Science

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Inhibition of the cyclin‐dependent kinase (CDK) 4/6‐retinoblastoma (RB) pathway is an effective therapeutic strategy against cancer. Here, we performed a preclinical investigation of the antitumor activity of SHR6390, a novel CDK4/6 inhibitor. SHR6390 exhibited potent antiproliferative activity against a wide range of human RB‐positive tumor cells in vitro, and exclusively induced G 1 arrest as well as cellular senescence, with a concomitant reduction in the levels of Ser780‐phosphorylated RB protein. Compared with the well‐known CDK4/6 inhibitor palbociclib, orally administered SHR6390 led to equivalent or improved tumor efficacy against a panel of carcinoma xenografts, and produced marked tumor regression in some models, in association with sustained target inhibition in tumor tissues. Furthermore, SHR6390 overcame resistance to endocrine therapy and HER2‐targeting antibody in ER‐positive and HER2‐positive breast cancer, respectively. Moreover, SHR6390 combined with endocrine therapy exerted remarkable synergistic antitumor activity in ER‐positive breast cancer. Taken together, our findings indicate that SHR6390 is a novel CDK4/6 inhibitor with favorable pharmaceutical properties for use as an anticancer agent.

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Section: Resultsmentioning

confidence: 99%

Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models

Long

et al. 2019

Cancer Science

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“…Cyclin‐dependent kinase 6 (Cdk6), as a catalytic subunit of protein kinase complex, is involved in the regulation of cell cycle . The inhibitors of Cdk6 were shown to be a promising agents in the treatment of various tumors via suppressing G1/S phases progression of the cell cycle. Cdk inhibition also upregulated immediate senescence of small cell lung cancer cell, and Cdk4/6 inhibitors were found to be effective on treatment of NSCLC .…”

Section: Introductionmentioning

confidence: 99%

lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6

Liu

Chen

et al. 2019

J of Cellular Biochemistry

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Growing evidence have shown the important regulation of lncRNAs (long noncoding RNAs) in non–small cell lung cancer (NSCLC). lncRNA hepatocyte nuclear factor 1 homeobox A (HNF1A)‐antisense RNA 1 (AS1), an “oncogene”, was reported to regulate human tumors progression. However, the molecular mechanism of HNF1A‐AS1 involved in the development of NSCLC is still under investigation. In the current study, we found that HNF1A‐AS1 was relatively upregulated in both NSCLC patient tissues and cell lines. Functional studies established that overexpression of HNF1A‐AS1 promoted cell proliferation, cell cycle, invasion, and migration of NSCLC cells in vitro. The promotion abilities of HNF1A‐AS1 on NSCLC cell progression were suppressed via knockdown of HNF1A‐AS1. miR‐149‐5p was then proved to be a novel target of HNF1A‐AS1, whose expression was negatively correlated with HNF1A‐AS1 in NSCLC patient tissues and cell lines. HNF1A‐AS1 increased the expression of cyclin‐dependent kinase 6 (Cdk6) via sponging with miR‐149‐5p. Gain‐ and loss‐of‐functional studies indicated that HNF1A‐AS1 promoted NSCLC progression partially through inhibition of miR‐363‐3p and induction of Cdk6. Subcutaneous xenotransplanted tumor model confirmed that interference of HNF1A‐AS1 suppressed the tumorigenic ability of NSCLC via upregulation of miR‐149‐5p and downregulation of Cdk6 in vivo. In conclusion, our findings clarified the biologic significance of the HNF1A‐AS1/miR‐149‐5p/Cdk6 axis in NSCLC progression and provided novel evidence that HNF1A‐AS1 may be a new potential therapeutic target for the treatment of NSCLC.

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“…Furthermore, in vivo study showed that trastuzumab combined with abemaciclib inhibited tumor growth more than either single agent (84). In another preclinical study, abemaciclib with trastuzumab significantly improved tumor growth inhibition and tumor regressions in xenografts progressing on trastuzumab alone (81). In a phase I study, one patient with hormone receptor-negative and HER2…”

Section: Her2 Tk Inhibitorsmentioning

confidence: 98%

“…CDK4/6 inhibitors have shown great potential in preclinical studies and clinical trials, such as palbocilcib and ribociclib which has been applied in clinical (79,80). Though CDK4/6 inhibitors are mainly used to treat estrogen receptor (ER) + /HER2 -patients, some studies found that they also have potential therapeutic effect on ER + /HER2 + patients (81). In an exploratory, open-label, phase 2 study (NA-PHER2), the combination of palbociclib, fulvestrant, trastuzumab and pertuzumab was found reduced the expression of Ki67 significantly (82).…”

Section: Her2 Tk Inhibitorsmentioning

confidence: 99%

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Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

et al. 2018

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Abstract.Human epidermal growth factor receptor-2 positive breast cancer (HER2 + BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2 + BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2 + BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2 + BC patients in the future.

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Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib

Cited by 171 publications

References 59 publications

Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models

Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models

lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

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