In silico repurposing of midostaurin as a therapeutic candidate for head and neck cancer via targeting SPARC/MMP9/CD44 Cancer-Associated Fibroblasts (CAFs) oncogenic signature

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Title:	In silico repurposing of midostaurin as a therapeutic candidate for head and neck cancer via targeting SPARC/MMP9/CD44 Cancer-Associated Fibroblasts (CAFs) oncogenic signature
Authors:	劉明哲 Lin, Kuan-Chou;Wu, Chia-Che;Mokgautsi, Ntlotlang;Lawal, Bashir;Wu, Ching-Zong;Wu, Alexander Th;Shen, Yung-Kang;Liu, Ming-Che
Contributors:	牙體技術學系
Keywords:	Head and neck squamous cancers (HNSCC);cancer-associated fibroblasts (CAFs);drug resistance;midostaurin;molecular docking
Date:	2023-03
Issue Date:	2024-12-04 14:04:59 (UTC+8)
Abstract:	Head and neck squamous carcinoma (HNSCC) affects more than half a million individuals and ranks the ninth leading cause of death globally each year. Many patients develop treatment resistance leading to poor clinical outcomes. The poor treatment responses are in part due to the heterogeneity of HNSCC tumor and tumor microenvironment (TME). The interaction of tumor cells with their TME has been studied vigorously in recent years because of their pivotal roles in tumorigenesis and determining the treatment response. Cancer-associated fibroblasts (CAFs) are one of the most abundant tumor-infiltrating cells; which have been shown to associate with the aggressive behavior of HNSCC. Hence; targeting and disrupting the tumor-CAFs interactions represents a rational therapeutic approach. To develop targeted therapeutic drugs against CAFs; the identification of CAF-associated gene signature is essential. Here; we analyzed multiple sequencing databases including microarrays and single-cell RNA-sequencing databases and identified SPARC/MMP9/CD44 as HNSCC targetable gene signatures encompassing cancer-associated fibroblasts (CAFs). We found SPARC/MMP9CD44 signature was highly expressed in HNSC tissues compared to adjacent normal tissues. Increased SPARC/MMP9/CD44 signature levels strongly correlated with tumor-infiltrating CAFs; suggesting the functional importance of this signature for HNSCC-CAFs interaction and progression. Subsequently; we utilized a genomics approach and identified midostaurin as the top-ranking drug candidate for targeting SPARC/MMP9/CD44 signature. For validation; we performed molecular docking of midostaurin in complex with SPARC/MMP9/CD44 and demonstrated midostaurin's high binding affinities compared to their respective standard inhibitors. In summary; our study provided a rapid genomics approach for identifying targetable gene signature and drug candidate for HNSCC.
Relation:	American journal of cancer research; 13(3); 1004–1025.
Description:	【112-2 升等】臺北醫學大學教師升等專門著作職別：專任送審等級：教授著作送審
Note:	代表著作名稱：《In silico repurposing of midostaurin as a therapeutic candidate for head and neck cancer via targeting SPARC/MMP9/CD44 Cancer-Associated Fibroblasts (CAFs) oncogenic signature》 AJCR Copyright ? 2023.
Data Type:	article
Appears in Collections:	[Scholarly output for promotion] 112 [School of Dental Technology] Periodical Articles

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