Quantifying Risk Pathway Crosstalk Mediated by miRNA to Screen Precision drugs for Breast Cancer Patients

Abstract

Breast cancer has become the most common cancer that leads to women’s death. Breast cancer is a complex, highly heterogeneous disease classified into various subtypes based on histological features, which determines the therapeutic options. System identification of effective drugs for each subtype remains challenging. In this work, we present a computational network biology approach to screen precision drugs for different breast cancer subtypes by considering the impact intensity of candidate drugs on the pathway crosstalk mediated by miRNAs. Firstly, we constructed and analyzed the subtype-specific risk pathway crosstalk networks mediated by miRNAs. Then, we evaluated 36 Food and Drug Administration (FDA)-approved anticancer drugs by quantifying their effects on these subtype-specific pathway crosstalk networks and combining with survival analysis. Finally, some first-line treatments of breast cancer, such as Paclitaxel and Vincristine, were optimized for each subtype. In particular, we performed precision screening of subtype-specific therapeutic drugs and also confirmed some novel drugs suitable for breast cancer treatment. For example, Sorafenib was applicable for the basal subtype treatment, Irinotecan was optimum for Her2 subtype treatment, Vemurafenib was suitable for the LumA subtype treatment, and Vorinostat could apply to LumB subtype treatment. In addition, the mechanism of these optimal therapeutic drugs in each subtype of breast cancer was further dissected. In summary, our study offers an effective way to screen precision drugs for various breast cancer subtype treatments. We also dissected the mechanism of optimal therapeutic drugs, which may provide novel insight into the precise treatment of cancer and promote researches on the mechanisms of action of drugs.

Bioética y medicina personalizada en el envejecimiento: explorar las complejidades

“…En un estudio para identificar posibles medicamentos de precisión para pacientes con cáncer de mama, Xu y colaboradores 42 analizaron la diafonía entre diferentes vías de riesgo mediadas por miARN. Usando herramientas bioinformáticas para analizar la expresión génica y los objetivos de miARN en el cáncer de mama, fueron capaces de identificar varios miARN que participaban en la regulación de las vías de riesgo y podrían ser objetivos potenciales para tratamientos con fármacos.…”

Bioética e medicina personalizada no envelhecimento: explorando complexidades

“…Em estudo para identificar potenciais medicamentos de precisão para pacientes com câncer de mama, Xu e colaboradores 42 analisaram a diafonia entre diferentes vias de risco mediadas por miRNA. Usando ferramentas de bioinformática para analisar a expressão gênica e os alvos de miRNA no câncer de mama, eles foram capazes de identificar vários miRNA que estavam envolvidos na regulação das vias de risco e poderiam ser alvos potenciais para tratamentos com drogas.…”

Bioethics and concierge medicine in aging: exploring complexities

“…In a study to identify potential precision drugs for breast cancer patients, Xu and collaborators 42 analyzed the diaphony between different miRNAmediated risk pathways. Using bioinformatics tools to analyze gene expression and miRNA targets in breast cancer, they identified several miRNAs involved in regulating risk pathways that could be potential targets for drug treatments.…”