Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms

Wang, Bin; Li, Rui; Liu, Xin; Ren, Jianlin; Li, Jing; Bi, Kaixin; Wang, Yanhong; Jia, Hong-Ti

doi:10.3389/fonc.2021.651541

Cited by 12 publications

(7 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Being a driver of G1/S transition, cyclin D1-CDK4/6 complex depletion, is likely to be implicated in the G0–G1 phase arrest. Generally speaking, eugenol mediated mitigation of CDK4/6 is expected to permit continuous retention of E2Fs transcription factors by the retinoblastoma tumor suppressor (RB) thus refraining cell cycle progression 47 . Besides, shortening in TFDP1 gene, a heterodimeric partner of activator E2F, will almost certainly inhibit DNA binding and activation of target genes 48 .…”

Section: Discussionmentioning

confidence: 99%

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Issa,

Loubaki,

Al Amri

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent.

show abstract

Section: Discussionmentioning

confidence: 99%

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Issa,

Loubaki,

Al Amri

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Firstly, abemaciclib does not provide benefit in all patients with HR + /HER2 − advanced breast cancer. Great efforts have been made to identify the mechanism of resistance to CDK4/6 inhibitors ( 42 , 43 ), however, no clear mechanism of resistance is sufficiently validated. The identification of specific biomarkers could help to identify patients who are more likely to respond to treatment of CDK4/6 inhibitors.…”

Section: Future Perspectivementioning

confidence: 99%

A narrative review of the clinical development of CDK4/6 inhibitor abemaciclib in breast cancer

Liu¹,

Yang²,

Wang³

et al. 2022

Transl Breast Cancer Res

View full text Add to dashboard Cite

Background and Objective: Advanced or metastatic breast cancer (MBC) is associated with poor prognosis and presents many challenges in medical management and treatment decisions. Anticancer drugs that act on cell cycle mechanisms have shown great potential in preclinical studies. In clinical trials, abemaciclib, a reversible ATP-competitive cyclin-dependent kinase 4/6 (CDK4/6) inhibitor developed by Eli Lilly and Company, combined with endocrine therapy (ET) were associated with superior outcomes compared with ET alone in patients with advanced or metastatic hormone receptor positive (HR + )/human epidermal growth factor receptor 2 negative (HER2 − ) breast cancer, representing a new standard-of-care in this population. Abemaciclib has been approved by the U.S. Food and Drug Administration (FDA) for use in HR + /HER2 − MBC. In China, abemaciclib was also approved by the National Medical Products Administration (NMPA) based on findings from the MONARCH plus trial. Recently, abemaciclib have been approved as the first and only CDK4/6 inhibitor by FDA and NMPA for use in HR + /HER2 − , node-positive, early breast cancer (EBC) at high risk of recurrence and Ki-67 score ≥20%. Further trials of abemaciclib are ongoing. This is an overview of the clinical development of abemaciclib in breast cancer. Methods: We reviewed English publications in PubMed related to CDK4/6 inhibitors from 2011 to 2021.

show abstract

“…Acquired resistance is the main reason for the therapeutic failure of CDK4/6 inhibitors in RB-proficient tumors, where tumor cells can acquire the ability to survive in the absence of CDK4/6 function [ 139 ]. Elucidation of the potential mechanisms of acquired resistance to CDK4/6 inhibitors may help to identify effective combination therapies to improve therapeutic responses to CDK4/6 inhibitors [ 87 ].…”

Section: Inhibition Of Cyclin-dependent Kinases 4/6 (Cdk4/6) As a Sou...mentioning

confidence: 99%

Precision Medicine Highlights Dysregulation of the CDK4/6 Cell Cycle Regulatory Pathway in Pediatric, Adolescents and Young Adult Sarcomas

Barghi

Shannon

Saadatzadeh

et al. 2022

Cancers

View full text Add to dashboard Cite

Despite improved therapeutic and clinical outcomes for patients with localized diseases, outcomes for pediatric and AYA sarcoma patients with high-grade or aggressive disease are still relatively poor. With advancements in next generation sequencing (NGS), precision medicine now provides a strategy to improve outcomes in patients with aggressive disease by identifying biomarkers of therapeutic sensitivity or resistance. The integration of NGS into clinical decision making not only increases the accuracy of diagnosis and prognosis, but also has the potential to identify effective and less toxic therapies for pediatric and AYA sarcomas. Genome and transcriptome profiling have detected dysregulation of the CDK4/6 cell cycle regulatory pathway in subpopulations of pediatric and AYA OS, RMS, and EWS. In these patients, the inhibition of CDK4/6 represents a promising precision medicine-guided therapy. There is a critical need, however, to identify novel and promising combination therapies to fight the development of resistance to CDK4/6 inhibition. In this review, we offer rationale and perspective on the promise and challenges of this therapeutic approach.

show abstract

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms

Cited by 12 publications

References 102 publications

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

A narrative review of the clinical development of CDK4/6 inhibitor abemaciclib in breast cancer

Precision Medicine Highlights Dysregulation of the CDK4/6 Cell Cycle Regulatory Pathway in Pediatric, Adolescents and Young Adult Sarcomas

Contact Info

Product

Resources

About