PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 27756261-0 2016 Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways. Lapatinib 78-87 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 118-121 28158234-12 2017 Pharmaceutical inhibition of Yes1 by the Src inhibitor dasatinib was also effective to restore the sensitivity to trastuzumab and lapatinib in the two resistant cell lines. Lapatinib 130-139 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 41-44 26643609-5 2016 Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and alpha-smooth muscle actin, accompanied by activation of nuclear factor-kB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Lapatinib 0-9 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 224-227 25865888-5 2015 Genetic and chemical inhibition of BET bromodomain chromatin readers suppresses transcription of many lapatinib-induced kinases involved in resistance, including ERBB3, IGF1R, DDR1, MET, and FGFRs, preventing downstream SRC/FAK signaling and AKT reactivation. Lapatinib 102-111 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 220-223 26621843-8 2016 These data indicate that erbB3 signaling is critical for both trastuzumab and lapatinib resistances mainly through the PI-3K/Akt pathway, whereas IGF-1R-initiated Src activation results in trastuzumab resistance without affecting lapatinib sensitivity. Lapatinib 230-239 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 163-166 25350844-0 2014 Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models. Lapatinib 30-39 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 0-3 25350844-8 2014 Genetic and pharmacologic inhibition of Src resensitized these subclones to lapatinib. Lapatinib 76-85 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 40-43 25350844-9 2014 Biochemically, Src mutations could activate both the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways in the lapatinib-treated LR OE19 cells. Lapatinib 136-145 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 15-18 24887236-0 2014 Epidermal growth factor-receptor activation modulates Src-dependent resistance to lapatinib in breast cancer models. Lapatinib 82-91 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 54-57 24887236-2 2014 To identify the mechanism by which Src overexpression sustains this resistance, we tested a panel of breast cancer cell lines either sensitive or resistant to lapatinib. Lapatinib 159-168 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 35-38 24887236-5 2014 We used artificial metastasis assays to evaluate the effect of Src inhibition on the invasiveness of lapatinib-resistant cells. Lapatinib 101-110 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 63-66 24887236-7 2014 RESULTS: Src activation was higher in lapatinib-resistant than in lapatinib-sensitive cells. Lapatinib 38-47 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 9-12 24887236-7 2014 RESULTS: Src activation was higher in lapatinib-resistant than in lapatinib-sensitive cells. Lapatinib 66-75 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 9-12 24887236-8 2014 The selective small-molecule Src inhibitor saracatinib combined with lapatinib synergistically inhibited the proliferation, migration, and invasion of lapatinib-resistant cells. Lapatinib 151-160 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 29-32 24887236-10 2014 Unexpectedly, in lapatinib-resistant cells, Src preferentially interacted with epidermal growth factor receptor (EGFR) rather than with HER2. Lapatinib 17-26 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 44-47 24887236-11 2014 Moreover, EGFR targeting and lapatinib synergistically inhibited survival, migration, and invasion of resistant cells, thereby counteracting Src-mediated resistance. Lapatinib 29-38 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 141-144 24887236-12 2014 These findings demonstrate that Src activation in lapatinib-resistant cells depends on EGFR-dependent rather than on HER2-dependent signaling. Lapatinib 50-59 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 32-35 24887236-13 2014 CONCLUSIONS: Complete pharmacologic EGFR/HER2 inhibition is required to reverse Src-dependent resistance to lapatinib in breast cancer. Lapatinib 108-117 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 80-83 34382727-5 2021 Furthermore, the upregulation of miR-221 was mediated by the lapatinib-induced Src family tyrosine kinase and subsequent NF-kB activations. Lapatinib 61-70 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 79-82 24200972-6 2014 Treatment with the Src inhibitor saracatinib in combination with lapatinib reduces AKT and ERK1/2 phosphorylation and restores the sensitivity of resistant cells to lapatinib. Lapatinib 165-174 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 19-22 24200972-10 2014 Taken together, our results demonstrate that breast cancer cells with acquired resistance to lapatinib have a more aggressive phenotype compared with their parental counterpart, and that Src signaling and CXCR4 play an important role in this phenomenon, thus representing potential targets for therapeutic intervention in lapatinib-resistant breast cancer patients. Lapatinib 93-102 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 187-190 24200972-10 2014 Taken together, our results demonstrate that breast cancer cells with acquired resistance to lapatinib have a more aggressive phenotype compared with their parental counterpart, and that Src signaling and CXCR4 play an important role in this phenomenon, thus representing potential targets for therapeutic intervention in lapatinib-resistant breast cancer patients. Lapatinib 322-331 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 187-190 23913825-6 2013 When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. Lapatinib 53-62 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 67-70 21499296-6 2011 Treatment of these resistant cells with Src kinase inhibitors partially blocked PI3K-Akt signaling and restored lapatinib sensitivity. Lapatinib 112-121 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 40-43 21499296-9 2011 These data suggest that increased Src kinase activity is a mechanism of lapatinib resistance and support the combination of HER2 antagonists with Src inhibitors early in the treatment of HER2+ breast cancers in order to prevent or overcome resistance to HER2 inhibitors. Lapatinib 72-81 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 34-37 24200972-0 2014 Src and CXCR4 are involved in the invasiveness of breast cancer cells with acquired resistance to lapatinib. Lapatinib 98-107 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 0-3 24200972-5 2014 Lapatinib-resistant cells have an increased Src kinase activity and persistent levels of activation of ERK1/2 and AKT compared with parental cells. Lapatinib 0-9 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 44-47 22389470-9 2012 In SBC-3/ETP cells, dephosphorylation of HER2 by lapatinib activates Src and successively leads to increased caveolin-1 phosphorylation. Lapatinib 49-58 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 69-72 34382727-7 2021 Our study not only identified miRNA-221 as a pivotal factor conferring the acquired resistance of HER2-positive breast cancer cells to lapatinib through negatively regulating p27kip1 expression but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance. Lapatinib 264-273 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 213-216 34382727-6 2021 The reversal of miR-221 upregulation and p27kip1 downregulation by Src inhibitor, dasatinib, can overcome lapatinib resistance. Lapatinib 106-115 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 67-70 34382727-7 2021 Our study not only identified miRNA-221 as a pivotal factor conferring the acquired resistance of HER2-positive breast cancer cells to lapatinib through negatively regulating p27kip1 expression but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance. Lapatinib 135-144 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 213-216