The discovery of lncRNAs has dramatically changed the understanding of the biology of human diseases, especially when genomic studies of tough-to-treat cancers have mainly focused on protein-coding genes and provided no effective targeted therapies. Many TNBC (triple negative breast cancer) patients poorly respond to chemotherapy and radiotherapy due to EGFR (epidermal growth factor receptor) gene amplification and TP53 mutations [60, 61]. Most recently, researchers have identified a lncRNA – LINP1 – that regulates the sensitivity of the tumor cells to radiation therapy (Figure 4A) . LINP1 was initially identified as overexpressed in TNBC when compared with other breast cancer subtypes using RNA-seq data from the Cancer Genome Atlas and the Cancer Cell Line Encyclopedia. Among the dozens of lncRNA candidates, LINP1 stands out as functional screening has revealed that LINP1 knockdown enhanced apoptosis in TNBC cell lines following doxorubicin treatment (a chemotherapy drug for TNBC) . By applying in-vitro synthesized and also endogenous RNA, the authors demonstrated that LINP1 transcript physically interacted with Ku80-DNA-PKcs complex. Therefore, LINP1 knockdown in TNBC cells led to reduced DSB repair, and conversely, overexpression of LINP1 in ER-positive cells increased NHEJ activity . The authors uncovered that EGFR activation upregulates LINP1 transcription, thus in turn stabilizes the Ku80-DNA-PKcs interaction. On the other hand, TP53 activation stimulates miR-29 that targets LINP1 and down-regulates its expression later point after damage. Thus, TP53 mutations in TNBC would further increase LINP1 expression at the post-transcriptional levels after DNA damage. Given that inhibition of the NHEJ pathway has been proposed by oncology researchers to synergize DNA-damaging therapies for better treatment outcomes for TNBC, LINP1, as a new class of cancer-driver gene that links two repair scaffold proteins, may serve as a novel therapeutic target for TNBC treatment. While this study mainly focused on TNBC, these findings have left an open question: to what extent cellular LINP1 expression levels indicate NHEJ functional status, since overexpression of LINP1 increases resistance to genotoxic insults and loss of expression of LINP1 may impair genome stability.