Kinase inhibitors for precision therapy of triple-negative breast cancer: Progress, challenges, and new perspectives on targeting this heterogeneous disease

Mehlich, Dawid; Marusiak, Anna A.

doi:10.1016/j.canlet.2022.215775

Cited by 14 publications

(7 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kinase inhibitors are also used to treat triple-negative breast cancer (TNBC), in which the survival rate is worse than in other subtypes of breast cancer [ 18 ]. Several treatment options are available, such as chemotherapy, immunotherapy, radiation therapy, and surgery.…”

Section: Overview Of Published Articlesmentioning

confidence: 99%

Cancer Therapy Resistance: Choosing Kinase Inhibitors

Dell’Aversana,

Sarno,

Benedetti

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

Section: Overview Of Published Articlesmentioning

confidence: 99%

Cancer Therapy Resistance: Choosing Kinase Inhibitors

Dell’Aversana,

Sarno,

Benedetti

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Thus inhibiting tumor immune system inactivation leads to immune activation to eliminate the TNBC cells. However, only approximately 40% of TNBC patients are eligible for immunotherapy 2 . Besides immunotherapy, targeting protein kinase provides other potential targeted therapies for TNBC patients.…”

Section: Introductionmentioning

confidence: 99%

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells

Satriyo,

Mustofa,

Wahyuningsih

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Protein kinase dysregulation induces cancer cell aggressiveness leading to rapid tumor progression and poor prognosis in TNBC patients. Many small-molecule kinase inhibitors have been tested in clinical trials to treat TNBC patients. In the previous study, we found that N-phenylpyrazoline small molecule acts as a protein kinase inhibitor in cervical cancer cells. However, there remains unknown about N-phenyl pyrazoline potency as a kinase inhibitor and its anti-cancer activity in TNBC cells. In this study, we investigated the activity of N-phenyl pyrazoline against TNBC cells via tyrosine kinase inhibition. Based on the MTT assay, the IC50 values for the N-phenyl pyrazoline 2, 5, A, B, C, and D against Hs578T were 12.63 µM, 3.95 µM, not available, 18.62 µM, 30.13 µM, and 26.79 µM, respectively. While only P5 exhibited the IC50 against MDA MB 231 (21.55 µM). Further, N-phenyl pyrazoline 5 treatment significantly inhibited the cell proliferation rate of Hs578T and MDA MB 231 cells. The migration assay showed that treatment with the compound N-phenyl pyrazoline 5 with 4 µM concentration significantly reduced cell migration of Hs578T cells. N-phenyl pyrazoline 5 treatment at 1 µM and 2 µM was able to reduce the tumorsphere size of Hs578t cells. A combination treatment of P5 and paclitaxel showed a synergistic effect with a combination index score > 1 in both TNBC cells. Further, the P5 predictively targeted the protein kinases that significantly correlated to breast cancer prognosis. The GSEA analysis result shows that receptor tyrosine kinase, Notch3, Notch4, and Ephrin signaling pathways were targeted by P5. The P5 treatment reduced the EGFR expression level and activation in TNBC cells.

show abstract

“…In recent years, a thesis has been put forward that dependent on various clinical, pathological, and genetic factors, triple-negative breast cancer is a separate, heterogenic subtype of breast cancer, ( 4 ). Multi-omics profiling studies have provided novel insights into the biological heterogeneity of TNBC, evolutionizing the classification of these tumors into distinct molecular subtypes based on recurrent genetic aberrations, transcriptional patterns, and tumor microenvironment features ( 5 ). Here, molecular typing together with the prediction of the prognosis of the gene profile may help to promote the study of personalized treatment.…”

Section: Introductionmentioning

confidence: 99%

The molecular subtypes of triple negative breast cancer were defined and a ligand-receptor pair score model was constructed by comprehensive analysis of ligand-receptor pairs

et al. 2022

View full text Add to dashboard Cite

BackgroundIntercellular communication mediated by ligand-receptor interactions in tumor microenvironment (TME) has a profound impact on tumor progression. This study aimed to explore the molecular subtypes mediated by ligand-receptor (LR) pairs in triple negative breast cancer (TNBC), identify the most important LR pairs to construct a prognostic risk model, and study their effect on TNBC immunotherapy.MethodsLR pairs subclasses of TNBC were categorized by consensus clustering based on LR Pairs in METABRIC dataset. Least absolute shrinkage and selection operator (LASSO) Cox regression and stepwise Akaike information criterion (stepAIC) were conducted to build a LR pairs score model. The relationship between LR pairs score and immune cell infiltration, stromal score and immune score associated with TME was analyzed, and the prediction of drug therapy and immunotherapy efficacy by LR pairs score was evaluated.ResultsAccording to the expression pattern of 145 TNBC prognostic LR pairs, the samples were divided into three subclasses with different survival outcomes, copy number variation (CNV), TME immune cell infiltration, stromal score and immune score. The LR pairs score model constructed in the METABRIC dataset was composed of four LR pairs, and its predictive significance for TNBC prognosis was verified in GSE58812 and GSE21653 cohorts. In addition, LR pairs score was negatively correlated with several immune pathways regulating immunity and immune score, and related to the sensitivity of anti-neoplastic drugs and the effect of anti-PD-L1 therapy.ConclusionOur study confirmed the impact of LR pairs on the molecular heterogeneity of TNBC, characterized three LR pairs subtypes with different survival outcomes and TME patterns, and proposed a LR pairs score system with predictive significance for TNBC prognosis and anti-PD-L1 therapeutic effect, which provides a potential evaluation scheme for TNBC management.

show abstract

Kinase inhibitors for precision therapy of triple-negative breast cancer: Progress, challenges, and new perspectives on targeting this heterogeneous disease

Cited by 14 publications

References 117 publications

Cancer Therapy Resistance: Choosing Kinase Inhibitors

Cancer Therapy Resistance: Choosing Kinase Inhibitors

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells

The molecular subtypes of triple negative breast cancer were defined and a ligand-receptor pair score model was constructed by comprehensive analysis of ligand-receptor pairs

Contact Info

Product

Resources

About