Role of CDK4/6 inhibitors in patients with hormone receptor (HR)-positive, human epidermal receptor-2 negative (HER-2) metastatic breast cancer study protocol for a systematic review, network meta-analysis and cost-effectiveness analysis

Hu, Quan; Kang, Wenli; Wang, Qingfeng; Luo, Ting

doi:10.1136/bmjopen-2021-056374

Cited by 4 publications

(3 citation statements)

References 71 publications

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“…Therefore, E receptor and P receptor are very important biological indicators of breast cancer. HER-2 protein is a transmembrane glycoprotein, which plays an important role in the process of cell proliferation, differentiation, and angiogenesis [ 23 ]. This high expression can accelerate cell division, make the process of proliferation and differentiation unbalanced, and finally turn into cancer cells.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Correlation Analysis of Ultrasound Elastography Score with Invasive Breast Cancer and Biological Prognostic Factors

Wan

Qin

et al. 2022

Contrast Media & Molecular Imaging

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Invasive breast cancer (IBC) is a kind of malignant tumor in which cancer cells have broken through the basement membrane of breast ducts or lobular acini and invaded the stroma. Although ultrasound elastography score (UES) has shown unique advantages in the diagnosis of IBC, its value in the prognosis is not clear. Here, we explored the correlation of UES with IBC and biological prognostic factors. The datum of 86 patients with suspected IBC from January 2018 to December 2021 was collected. UE was applied in the examination of all patients. The lesion tissue of the malignant group was punctured to detect and analyze the expression of biological prognostic factors, including estrogen receptor (E receptor), progesterone receptor (P receptor), and human epidermal growth factor 2 (HER factor 2) and Ki67. The differences in UES under different biological prognostic factors were compared. The receiver operating characteristic (ROC) curve was applied to analyze the diagnostic value of UES of IBC and the expression of biological prognostic factors. Based on the pathological diagnosis results, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of UES in the diagnosis of IBC were analyzed. The correlation of UES with IBC and biological prognostic factors was analyzed by multiple linear regression and Spearman method. ROC analysis showed that the area under the curve of UES for diagnosing IBC and evaluating the expression of P receptor, HER factor 2, and Ki67 were 0.877, 0.704, 0.763, and 0.820, respectively (P＜0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of UES when diagnosing IBC were 92.42%, 90.00%, 91.86%, 96.83%, and 78.26%, respectively. The UES of E receptor expression (positive and negative group) showed no obvious variance ( P > 0.05). The UES of P receptors (positive and negative), HER factor 2 (positive and negative), and Ki67 (high and low expression) showed obvious differences ( P < 0.05). Multiple linear regression and Spearman indicated UES was significantly correlated with the expression of P receptor, HER factor 2, and Ki67 (P＜0.05). UES has a certain diagnostic value for IBC and is significantly correlated to the expression of P receptor, HER factor 2, and Ki67, which is helpful for evaluating the prognosis of patients with IBC.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Correlation Analysis of Ultrasound Elastography Score with Invasive Breast Cancer and Biological Prognostic Factors

Wan

Qin

et al. 2022

Contrast Media & Molecular Imaging

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“…The issue of cost-effectiveness remains critical in oncology to ensure the sustainability of treatments. [21] The cost-effectiveness of CDK4/6 inhibitors for the treatment of HR+/ HER2− advanced breast cancer has been analyzed in some of the literature, [22][23][24][25][26][27] but the results of the literature may be different from the results of the scores in this evaluation. The reason is that the results of cost-effectiveness analysis in other countries cannot be directly applied to the selection of CDK4/6 inhibitors by Chinese medical institutions.…”

Section: Discussionmentioning

confidence: 99%

CDK4/6 inhibitors for hormone receptor-positive/human epidermal growth factor receptor 2 negative advanced breast cancer: A rapid health technology assessment

Gu,

Chen,

Xie

et al. 2023

Medicine

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Object: Based on the best available evidence, rapid health technology was used to assess 4 CDK4/6 inhibitors approved for marketing in China. This assessment aims to provide a reference basis for the selection of drugs by medical institutions in China and to promote the rational use of drugs in the clinic. Methods: Depending on the Rapid Guidelines for Drug Evaluation and Selection in Chinese Medical Institutions (the Second Edition), a percentage quantitative scoring approach was used to objectively score the pharmacological properties, efficacy, safety, economy, and other attributes of CDK4/6 inhibitors. Results: The composite score rankings were, in descending order, 78.09 points for abemaciclib, 78.04 points for palbociclib, 72.15 points for dalpiciclib, and 69.24 points for ribociclib by integrating the result of the 5 dimensions. Conclusion: Until the clinical studies, guideline recommendations, prices, and many other aspects of this assessment are updated, abemaciclib and palbociclib, which have the top 2 scores, can be used as a priority recommendation for Chinese medical institutions to select CDK4/6 inhibitors and optimize the use of the drug catalog based on the scoring results of this assessment.

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“…Thus, has become the cornerstone of treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative metastatic breast cancer [11]. This combined approach has significantly delayed disease progression and improved overall survival rates [12].…”

Section: Introductionmentioning

confidence: 99%

Repurposing of approved drugs for targeting CDK4/6 and aromatase protein using molecular docking and molecular dynamics studies

yousif,

Alzain,

Alraih

et al. 2023

PLoS ONE

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Breast cancer is a leading cause of cancer-related morbidity and mortality worldwide, with the highest incidence among women. Among the various subtypes of breast cancer, estrogen-receptor positive (ER+) is the most diagnosed. Estrogen upregulates cyclin D1, which in turn promotes the activity of CDK4/6 and facilitates cell cycle progression. To address this, the first-line treatment for ER+ breast cancer focuses on inhibiting estrogen production by targeting aromatase, the enzyme responsible for the rate-limiting step in estrogen synthesis. Thus, combining CDK4/6 inhibitors with aromatase inhibitors has emerged as a crucial treatment strategy for this type of breast cancer. This approach effectively suppresses estrogen biosynthesis and controls uncontrolled cell proliferation, significantly improving overall survival rates and delayed disease progression. This study aimed to identify compounds that are likely to inhibit CDK4/6 and aromatase simultaneously by using a structure-based drug design strategy. 12,432 approved and investigational drugs were prepared and docked into the active site of CDK6 using HTVS and XP docking modes of Glide resulting in 277 compounds with docking scores ≤ -7 kcal/mol. These compounds were docked into aromatase enzyme using XP mode to give seven drugs with docking scores≤ -6.001 kcal/mol. Furthermore, the shortlisted drugs were docked against CDK4 showing docking scores ranging from -3.254 to -8.254 kcal/mol. Moreover, MM-GBSA for the top seven drugs was calculated. Four drugs, namely ellagic acid, carazolol, dantron, and apomorphine, demonstrated good binding affinity to all three protein targets CDK4/6 and aromatase. Specifically, they exhibited favourable binding free energy with CDK6, with values of -51.92, -53.90, -50.22, and -60.97 kcal/mol, respectively. Among these drugs, apomorphine displayed the most favourable binding free energy with all three protein targets. To further evaluate the stability of the interaction, apomorphine was subjected to a 100 ns molecular dynamics simulation with CDK6. The results indicated the formation of a stable ligand-protein complex. While the results obtained from the MM-GBSA calculation of the binding free energies of the MD conformations of apomorphine showed less favourable binding free energy compared to that obtained post-docking. All these computational findings will provide better structural insight for the development of CDK4/6 and aromatase multi-target inhibitors.

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Role of CDK4/6 inhibitors in patients with hormone receptor (HR)-positive, human epidermal receptor-2 negative (HER-2) metastatic breast cancer study protocol for a systematic review, network meta-analysis and cost-effectiveness analysis

Cited by 4 publications

References 71 publications

[Retracted] Correlation Analysis of Ultrasound Elastography Score with Invasive Breast Cancer and Biological Prognostic Factors

[Retracted] Correlation Analysis of Ultrasound Elastography Score with Invasive Breast Cancer and Biological Prognostic Factors

CDK4/6 inhibitors for hormone receptor-positive/human epidermal growth factor receptor 2 negative advanced breast cancer: A rapid health technology assessment

Repurposing of approved drugs for targeting CDK4/6 and aromatase protein using molecular docking and molecular dynamics studies

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