PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34399705-9 2021 Furthermore, in vitro and in vivo pharmacological study has shown that lapatinib resistance by the loss of function of CSK or PTEN, could be overcome by lapatinib combined with the PI3K inhibitor copanlisib and MEK inhibitor trametinib. Lapatinib 71-80 mitogen-activated protein kinase kinase 7 Homo sapiens 211-214 34159337-6 2021 In human lung organoids, lapatinib protects from SARS-CoV-2-induced activation of pathways implicated in non-infectious acute lung injury and fibrosis downstream of ErbBs (p38-MAPK, MEK/ERK, and AKT/mTOR), pro-inflammatory cytokine production, and epithelial barrier injury. Lapatinib 25-34 mitogen-activated protein kinase kinase 7 Homo sapiens 182-185 29156708-8 2017 In HCC1954, the most refametinib-sensitive cell line (IC50= 397 nM), lapatinib treatment inhibits phosphorylation of MEK and MAPK but activates AKT phosphorylation, in contrast to the other 2 parental cell lines tested (BT474-P, SKBR3-P), suggesting that HER2 may directly activate MEK/MAPK and not PI3K/AKT in HCC1954 cells but not in the other 2 cell lines, perhaps explaining the refametinib-sensitivity of this cell line. Lapatinib 69-78 mitogen-activated protein kinase kinase 7 Homo sapiens 282-285 29156708-8 2017 In HCC1954, the most refametinib-sensitive cell line (IC50= 397 nM), lapatinib treatment inhibits phosphorylation of MEK and MAPK but activates AKT phosphorylation, in contrast to the other 2 parental cell lines tested (BT474-P, SKBR3-P), suggesting that HER2 may directly activate MEK/MAPK and not PI3K/AKT in HCC1954 cells but not in the other 2 cell lines, perhaps explaining the refametinib-sensitivity of this cell line. Lapatinib 69-78 mitogen-activated protein kinase kinase 7 Homo sapiens 117-120 29156708-10 2017 The combination of MEK inhibition (MEKi) with refametinib and copanlisib led to synergistic inhibition of growth in 4/6 cell lines tested (CI @ED75 = 0.39-0.75), whilst the combinations of lapatinib and refametinib led to synergistic inhibition of growth in 3/6 cell lines (CI @ED75 = 0.39-0.80). Lapatinib 189-198 mitogen-activated protein kinase kinase 7 Homo sapiens 19-22 25596742-7 2015 Under hypoxia, activation of ERK signaling is required for lapatinib resistance as treatment with MEK inhibitor trametinib reverses hypoxia-mediated lapatinib resistance. Lapatinib 59-68 mitogen-activated protein kinase kinase 7 Homo sapiens 98-101 28423638-4 2017 Herein, we showed that lapatinib prevented MAPK rebound and sensitized BRAFV600E-positive papillary thyroid cancer cells to BRAF/MEK inhibitors. Lapatinib 23-32 mitogen-activated protein kinase kinase 7 Homo sapiens 129-132 26081723-8 2015 Moreover, combination therapy with trametinib and lapatinib can exhibit a synergistic effect and may contribute to overcoming the resistance to MEK inhibitors. Lapatinib 50-59 mitogen-activated protein kinase kinase 7 Homo sapiens 144-147 28744398-6 2017 In the current study, we found that repeated treatment of HER2+ breast cancer cells with HER1/2 inhibitor Lapatinib led to increased phosphorylation of RAF, MEK, and ERK, while suppressing HER1 phosphorylation and reduced the active form of Ras, indicating existence of factor(s) activating RAF/MEK/ERK by bypassing RAS activation. Lapatinib 106-115 mitogen-activated protein kinase kinase 7 Homo sapiens 157-160 28744398-6 2017 In the current study, we found that repeated treatment of HER2+ breast cancer cells with HER1/2 inhibitor Lapatinib led to increased phosphorylation of RAF, MEK, and ERK, while suppressing HER1 phosphorylation and reduced the active form of Ras, indicating existence of factor(s) activating RAF/MEK/ERK by bypassing RAS activation. Lapatinib 106-115 mitogen-activated protein kinase kinase 7 Homo sapiens 295-298 28744398-10 2017 Together, these results suggest that chronic inhibition of the HER1/2 by Lapatinib triggers a feedback loop to activate RAF/MEK/ERK pathway, in a FOXO dependent but Ras-independent manner. Lapatinib 73-82 mitogen-activated protein kinase kinase 7 Homo sapiens 124-127 25596742-7 2015 Under hypoxia, activation of ERK signaling is required for lapatinib resistance as treatment with MEK inhibitor trametinib reverses hypoxia-mediated lapatinib resistance. Lapatinib 149-158 mitogen-activated protein kinase kinase 7 Homo sapiens 98-101 21464044-2 2011 Lapatinib is an EGFR/HER2 kinase inhibitor suppressing signaling through the RAS/RAF/MEK (MAP/ERK kinase)/MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase)/AKT pathways. Lapatinib 0-9 mitogen-activated protein kinase kinase 7 Homo sapiens 85-88 23531216-0 2013 MEK inhibition increases lapatinib sensitivity via modulation of FOXM1. Lapatinib 25-34 mitogen-activated protein kinase kinase 7 Homo sapiens 0-3 23531216-6 2013 Our current results indicate that MEK inhibition increases lapatinib-mediated cytotoxicity in resistant HER2-overexpressing breast cancer cells. Lapatinib 59-68 mitogen-activated protein kinase kinase 7 Homo sapiens 34-37 23531216-9 2013 In addition, Western blots, immunofluorescence, and immunohistochemistry demonstrated that the combination of MEK inhibitor plus lapatinib reduced nuclear expression of the MEK/ERK downstream proto-oncogene FOXM1. Lapatinib 129-138 mitogen-activated protein kinase kinase 7 Homo sapiens 173-176 23531216-11 2013 Finally, xenograft studies demonstrated that combined pharmacological inhibition of MEK plus lapatinib suppressed tumor growth and reduced expression of FOXM1 in HER2-overexpressing breast cancers that are resistant to trastuzumab and lapatinib. Lapatinib 235-244 mitogen-activated protein kinase kinase 7 Homo sapiens 84-87 25449780-5 2015 The combination of FW-04-806 and lapatinib showed synergistic reduction of HER2 expression and the downstream PI3K/Akt and Ras/MEK/ERK pathways, enhanced suppression of Akt-mediated FOXO3a inactivation and augmented antitumor efficacy on SKBR3 xenografts with a favorable toxicity profile, suggesting its viability as a combination therapy for clinical studies in HER2+ breast cancer patients. Lapatinib 33-42 mitogen-activated protein kinase kinase 7 Homo sapiens 127-130 23441129-0 2013 Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib. Lapatinib 199-208 mitogen-activated protein kinase kinase 7 Homo sapiens 82-85 21499301-4 2011 Lapatinib induced apoptosis in association with upregulation of the pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM) through inhibition of the MEK-ERK signaling pathway in breast cancer cells with HER2 amplification. Lapatinib 0-9 mitogen-activated protein kinase kinase 7 Homo sapiens 163-166 20088787-0 2010 Ras-induced resistance to lapatinib is overcome by MEK inhibition. Lapatinib 26-35 mitogen-activated protein kinase kinase 7 Homo sapiens 51-54 20088787-6 2010 Importantly, we found that resistance to lapatinib due to ras overexpression or to ras V12 is overcome by MEK inhibition with U0126, suggesting a key role for the MEK-Erk pathway in ras-induced resistance. Lapatinib 41-50 mitogen-activated protein kinase kinase 7 Homo sapiens 106-109 20088787-6 2010 Importantly, we found that resistance to lapatinib due to ras overexpression or to ras V12 is overcome by MEK inhibition with U0126, suggesting a key role for the MEK-Erk pathway in ras-induced resistance. Lapatinib 41-50 mitogen-activated protein kinase kinase 7 Homo sapiens 163-166 20088787-9 2010 Combining MEK inhibitors with lapatinib may help overcome this form of resistance and increase the efficacy of lapatinib in these tumors. Lapatinib 111-120 mitogen-activated protein kinase kinase 7 Homo sapiens 10-13 19853943-0 2009 Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK. Lapatinib 13-22 mitogen-activated protein kinase kinase 7 Homo sapiens 115-118 19853943-0 2009 Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK. Lapatinib 13-22 mitogen-activated protein kinase kinase 7 Homo sapiens 252-255 19853943-0 2009 Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK. Lapatinib 193-202 mitogen-activated protein kinase kinase 7 Homo sapiens 252-255 19853943-8 2009 CONCLUSIONS: These data suggest that radiosensitization by lapatinib is mediated largely through inhibition of MEK/ERK and that direct inhibition of this pathway may provide an additional avenue of radiosensitization in EGFR+ or HER2+ breast cancers. Lapatinib 59-68 mitogen-activated protein kinase kinase 7 Homo sapiens 111-114