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The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer.

ABSTRACT: Breast cancer (BC) is a heterogenous disease, with prognosis and treatment options depending on Estrogen, Progesterone receptor, and Human Epidermal Growth Factor Receptor-2 (HER-2) status. HER-2 negative, endocrine-independent BC presents a significant clinical challenge with limited treatment options. To date, promising strategies like immune checkpoint inhibitors have not yielded breakthroughs in patient prognosis. Despite being considered archaic, agents derived from natural sources, mainly plants, remain backbone of current treatment. In this context, we critically analyze novel naturally-derived drug candidates, elucidate their intricate mechanisms of action, and evaluate their pre-clinical in vitro and in vivo activity in endocrine-independent HER-2 negative BC. Since pre-clinical research success often does not directly correlate with drug approval, we focus on ongoing clinical trials to uncover current trends. Finally, we demonstrate the potential of combining cutting-edge technologies, such as antibody-drug conjugates or nanomedicine, with naturally-derived agents, offering new opportunities that utilize both traditional cytotoxic agents and new metabolites.

SUBMITTER: Puskulluoglu M

PROVIDER: S-EPMC10944949 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer.

Püsküllüoğlu Mirosława M Michalak Izabela I

Frontiers in pharmacology 20240304

Breast cancer (BC) is a heterogenous disease, with prognosis and treatment options depending on Estrogen, Progesterone receptor, and Human Epidermal Growth Factor Receptor-2 (HER-2) status. HER-2 negative, endocrine-independent BC presents a significant clinical challenge with limited treatment options. To date, promising strategies like immune checkpoint inhibitors have not yielded breakthroughs in patient prognosis. Despite being considered archaic, agents derived from natural sources, mainly ...[more]

PMID: 38500769

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Project description:PurposeTriple-negative breast cancer (TNBC) is an aggressive tumor with poor prognosis, it has higher recurrence and metastatic rates than other breast cancer subtypes. This study aims to investigate biomarkers and potential targets for TNBC related to ferroptosis through data mining and bioinformatics analysis. The findings may provide new insights for treating TNBC.MethodsThe TNBC patients' data from the Cancer Genome Atlas (TCGA) database were extracted for differential expression and prognosis analysis. Consensus genes obtained by intersecting differential expressed and ferroptosis-related genes was used to establish the prognostic model by the univariate and multivariate Cox analyses. Besides, TNBC data from the Gene Expression Omnibus (GEO) database was used to confirm the reliability of the prognosis model. Moreover, clinical information was analyzed by multifactorial independent analysis to identify independent prognostic factors. The expression of genes constituting the prognostic model was further validated using the Human Protein Atlas (HPA) database. Finally, the Comparative Toxicogenomic Data (CTD) database was used to explore possible treatment drugs for TNBC.ResultsWe obtained 13,245 differential expressed genes, and 177 consensus genes. 98 genes with prognostic implication were obtained by univariable Cox. Then, a prognostic model including 12 ferroptosis-related genes was constructed by multivariable Cox. The area under curve (AUC) value of the prognostic model for TNBC was 0.82. The GEO database validated that the model (AUC = 0.77) could predict the patient outcomes. The staining results of 10 out of 12 prognostic model genes in HPA database showed that their expression was consistent with our predictions. Clinical risk analysis indicated that risk score of patients could act as an independent prognostic factor. Finally, six drugs that may have interaction with 12 ferroptosis-related genes were obtained using the CTD database.ConclusionThe prognostic model composed of 12 ferroptosis-related genes could predict the prognosis of TNBC patients, and seven genes (ASNS, LAMP2, CAV1, DPP4, HELLS, TF, ZFP69B) could be potential new therapeutic targets for TNBC, and two drugs (1-methyl-3-isobutylxanthine, rosiglitazone) could act as potential therapeutic drugs for the treatment of TNBC.

Dataset Information

The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer.

Publications

The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer.

Similar Datasets

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