Cotargeting the lncRNA-PIP3 Interaction and AKT/PI3K Signaling Axis: A Novel Paradigm for Treating Triple-Negative Breast Cancer
Technical Report,15 Sep 2016,14 Sep 2017
University of Texas MD Anderson Center Houston United States
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Patients with triple-negative breast cancer TNBC have a high incidence of early relapse and metastasis currently, chemotherapy and targeted therapies are the main treatment modalities for TNBC, but one-third of patients develop recurrence and drug resistance within 3 years of therapy. Recently, we have discovered that LINK-A Lipid-Interacting Noncoding RNA for Kinase Activation, a breast cancer-upregulated lncRNA, interacts with PtdIns 3,4,5P3. In vitro and in vivo experiments demonstrated that LINK-A is critical for breast cancer cell invasiveness and metastasis via its functional role in regulating the PI3K-AKT signaling pathway. Importantly, the pan-cancer analysis of LINK-A expression in TCGA reveals strong correlation with TNBC and its potential for metastasis. One important goal of the proposed study would be to establish LINK-A as a novel prognostic biomarker that can reliably stratify patients with TNBC according to clinical outcomes. With the aim to work on precision medicine, we propose to investigate a novel lncRNA-dependent noncanonical PI3K-AKT pathway underlying the metastatic progression of TNBC. Therefore, combinations of PI3K-AKT pathway inhibitors with a LNA-based lncRNA targeting strategy tested in this application may deliver maximum efficacy intreating breast cancer metastasis.
- Medicine and Medical Research