PMID-sentid	Pub_year	Sent_text		comp_official_name	comp_offsetprotein_name	organism	prot_offset
26245675-8	2015	For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06).	Lapatinib	40-49	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	88-94	
29701763-0	2018	PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab.	Lapatinib	197-206	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-6	
28478451-0	2017	Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab.	Lapatinib	91-100	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	64-70	
29110152-0	2018	Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer.	Lapatinib	71-80	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	20-26	
27177864-0	2016	PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab.	Lapatinib	197-206	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-6	
26920887-8	2016	PIK3CA mutations were associated with shorter median PFS (mutant vs. wild type: 4.3 vs. 6.4 months) and OS (17.3 vs. 27.8 months) in capecitabine plus lapatinib-treated patients, but not in T-DM1-treated patients (PFS, 10.9 vs. 9.8 months; OS, not reached in mutant or wild type).	Lapatinib	151-160	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-6	
25199759-11	2014	In patients with PIK3CA mutation, the pCR rates were 16%, 24.3%, and 17.4% with lapatinib, trastuzumab, and the combination, respectively (P = .654) and in the wild-type group, they were 18.2%, 33.%, and 37.1%, respectively (P = .017).	Lapatinib	80-89	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	17-23	
26281684-2	2015	PIK3CA mutations are the predictive markers for anti-EGFR antibodies, trastuzumab, and lapatinib.	Lapatinib	87-96	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-6	
25559818-5	2015	Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012).	Lapatinib	55-64	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	83-89	
25559818-5	2015	Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012).	Lapatinib	55-64	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	219-225	
26181325-3	2015	We observed that combinations of lapatinib plus AKTi were synergistic in HER2(+)/PIK3CA(mut) cell lines but not in HER2(+)/PIK3CA(wt) cell lines.	Lapatinib	33-42	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	81-87	
26181325-5	2015	This revealed that p-S6RP levels were less well attenuated by lapatinib in HER2(+)/PIK3CA(mut) cells compared to HER2(+)/PIK3CAwt cells and that lapatinib + AKTi reduced p-S6RP levels to those achieved in HER2(+)/PIK3CA(wt) cells with lapatinib alone.	Lapatinib	62-71	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	83-89	
26181325-6	2015	We also found that that compensatory up-regulation of p-HER3 and p-HER2 is blunted in PIK3CA(mut) cells following lapatinib + AKTi treatment.	Lapatinib	114-123	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	86-92	
26181325-8	2015	We used a nonlinear ordinary differential equation model to support the idea that PIK3CA mutations act as downstream activators of AKT that blunt lapatinib inhibition of downstream AKT signaling and that the effects of PIK3CA mutations can be countered by combining lapatinib with an AKTi.	Lapatinib	146-155	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	82-88	
25195596-6	2014	We validated the top ranking genes, i.e., PIK3CA and PIK3CB, by showing that their forced expression confers resistance to lapatinib in vitro and found that their mutation/overexpression is associated to poor prognosis in human breast tumors.	Lapatinib	123-132	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	42-48	
25056500-7	2014	In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179).	Lapatinib	34-43	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	7-13	
25056500-7	2014	In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179).	Lapatinib	34-43	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	240-246	
24590635-14	2014	Our secondary end point findings of a significant correlation between PIK3CA mutation and response to letrozole-lapatinib in HR-positive/HER2-negative early breast cancer must now be independently confirmed.	Lapatinib	112-121	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	70-76	
21499301-6	2011	The pro-apoptotic effect of lapatinib was less pronounced in cells with a PIK3CA mutation than in those without one.	Lapatinib	28-37	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	74-80	
23633485-7	2013	However, the p110alpha-specific inhibitor BYL719 in combination with lapatinib impaired mammary tumor growth and PI3K signaling more potently than BYL719 alone.	Lapatinib	69-78	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	13-22	
24249715-0	2014	Enhanced PI3K p110alpha signaling confers acquired lapatinib resistance that can be effectively reversed by a p110alpha-selective PI3K inhibitor.	Lapatinib	51-60	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	14-23	
24249715-0	2014	Enhanced PI3K p110alpha signaling confers acquired lapatinib resistance that can be effectively reversed by a p110alpha-selective PI3K inhibitor.	Lapatinib	51-60	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	110-119	
24249715-3	2014	Genomic and proteomic analyses revealed that lapatinib-resistant breast cancer cells gained additional phosphoinositide 3-kinase (PI3K) activation through activating mutation in PI3K p110alpha and/or increasing protein expression of existing mutant p110alpha.	Lapatinib	45-54	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	183-192	
24249715-3	2014	Genomic and proteomic analyses revealed that lapatinib-resistant breast cancer cells gained additional phosphoinositide 3-kinase (PI3K) activation through activating mutation in PI3K p110alpha and/or increasing protein expression of existing mutant p110alpha.	Lapatinib	45-54	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	249-258	
24249715-4	2014	p110alpha protein upregulation in lapatinib-resistant cells occurred through gene amplification or posttranscriptional upregulation.	Lapatinib	34-43	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-9	
24249715-5	2014	Knockdown of p110alpha, but not p110beta, the other PI3K catalytic subunit present in epithelial cells, inhibited proliferation of lapatinib-resistant cells, especially when combined with lapatinib.	Lapatinib	131-140	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	13-22	
24249715-5	2014	Knockdown of p110alpha, but not p110beta, the other PI3K catalytic subunit present in epithelial cells, inhibited proliferation of lapatinib-resistant cells, especially when combined with lapatinib.	Lapatinib	188-197	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	13-22	
24249715-8	2014	These findings indicate that lapatinib resistance can occur through p110alpha protein upregulation-mediated, and/or mutation-induced, PI3K activation.	Lapatinib	29-38	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	68-77	
21499301-8	2011	Depletion of PIK3CA (a catalytic subunit of PI3K) revealed that survivin expression is regulated by the PI3K pathway in these cells, suggesting that insufficient inhibition of PI3K-survivin signaling is responsible for the limited pro-apoptotic effect of lapatinib in HER2 amplification-positive cells with a PIK3CA mutation.	Lapatinib	255-264	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	13-19	
21499301-9	2011	Consistent with this notion, depletion of survivin by RNAi or treatment with a PI3K inhibitor markedly increased the level of apoptosis in PIK3CA mutant cells treated with lapatinib.	Lapatinib	172-181	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	139-145	
21293538-14	2010	PTEN loss and PIK3CA gene mutations are other markers that may predict lapatinib poor response.	Lapatinib	71-80	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	14-20	
21676217-12	2011	PI3K pathway activation resulting from PTEN loss or PIK3CA mutations may lead to drug resistance to lapatinib and trastuzumab.	Lapatinib	100-109	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	52-58	
19844234-10	2009	Patients with tumours harbouring an H1047R PIK3CA mutation or low expression of PTEN derived clinical benefit from lapatinib.	Lapatinib	115-124	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	43-49	
19010894-0	2008	Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235.	Lapatinib	57-66	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-29	
19010894-0	2008	Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235.	Lapatinib	57-66	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	107-136	
19010894-5	2008	In addition, we show that two dominant activating mutations in PIK3CA (E545K and H1047R), which are prevalent in breast cancer, also confer resistance to lapatinib.	Lapatinib	154-163	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	63-69	
19010894-6	2008	Furthermore, we show that phosphatidylinositol 3-kinase (PI3K)-induced lapatinib resistance can be abrogated through the use of NVP-BEZ235, a dual inhibitor of PI3K/mTOR.	Lapatinib	71-80	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	26-55	
19010894-7	2008	Our data show that deregulation of the PI3K pathway, either through loss-of-function mutations in PTEN or dominant activating mutations in PIK3CA, leads to lapatinib resistance, which can be effectively reversed by NVP-BEZ235.	Lapatinib	156-165	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	139-145	
32988919-7	2020	CONCLUSION: Mutations in TP53 and PIK3CA hotspot at exon 9 may be potential negative predictors of ER+HER2+ BC treated with neoadjuvant letrozole and lapatinib, while MLL2 inactivating mutation might confer therapeutic benefit in these patients.	Lapatinib	150-159	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	34-40	
33005299-8	2020	Finally, a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression, which may explain the acquired resistance to lapatinib.	Lapatinib	185-194	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	11-81	
30624609-0	2019	PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab.	Lapatinib	197-206	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	0-6