Publication
Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235.
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- PubMed
- Retrieved
- Sep 8, 2026
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- normalized (units and labels harmonized; values unchanged)
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- ING-CIVIC-20260908-000001
Abstract
Abstract (excerpt)
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Linked entities
Linked entities (12)
How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.
Validated 12
- cancerHER2-Positive Breast Carcinomacivic_curation1.00
- drugDactolisibcivic_curation1.00
- drugLapatinibcivic_curation1.00
- drugTrastuzumabcivic_curation1.00
- genePIK3CAcivic_curation1.00
- genePTENcivic_curation1.00
- variantPIK3CA Amplificationcivic_curation1.00
- variantPIK3CA E545Kcivic_curation1.00
- variantPIK3CA H1047Rcivic_curation1.00
- variantPIK3CA K111Ncivic_curation1.00
- variantPIK3CA Overexpressioncivic_curation1.00
- variantPTEN Underexpressioncivic_curation1.00
Curated evidence
Evidence citing this paper (29)
- Source
- CIViC — Clinical Interpretation of Variants in Cancer
- Dataset
- CIViC evidence items
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- civic-2026-09-08
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Evidence
- expert curation
- License
- CC0 1.0
- PMID
- 19010894
- Run
- ING-CIVIC-20260908-000001
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| PIK3CA Amplification3 | ||||||||
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8272In a preclinical study, efficacy of NVP-BEZ235 (dactolisib) and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirally induced PI… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8273In a preclinical study, efficacy of NVP-BEZ235 (dactolisib), lapatinib, and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirall… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + LapatinibSubstitutes | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8271This preclinical study tested the sensitivity of HER2-positive breast cancer cell line BT-474 (heterozygous for PIK3CA K111N) retrovirally transduced with wildtype PIK3CA to NVP-BEZ235 (dactolisib; a … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PIK3CA E545K7 | ||||||||
| Dactolisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 3 | accepted | EID6213This preclinical study tested the sensitivity of HER2-positive breast cancer cell line BT-474 (heterozygous for PIK3CA K111N) retrovirally transduced with PIK3CA E545K to NVP-BEZ235 (dactolisib; a dua… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8180In a preclinical study, efficacy of trastuzumab and NVP-BEZ235 (dactolisib) combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirally induced PI… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6207This preclinical study tested, in vitro, the resistance to lapatinib (an anti-HER2 drug) of HER2-positive breast cancer cell lines (BT474 and SKBR3) retrovirally transduced with E545K. The study found… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 2 | submitted | EID6212This preclinical study tested the sensitivity of HER2-positive breast cancer cell line BT-474 (heterozygous for PIK3CA K111N) retrovirally transduced with PIK3CA E545K to NVP-BEZ235 (dactolisib; a dua… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6211In a preclinical study, efficacy of lapatinib and trastuzumab was evaluated in vitro against HER2 amplified breast cancer cell lines BT474 (heterozygous for PIK3CA K111N) or SKBR3, retrovirally transd… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6209This preclinical study tested, in vitro, the resistance to trastuzumab (an anti-HER2 drug) of HER2-positive cell lines (BT474 and SKBR3) retrovirally transduced with E545K. The study found that the E5… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8181In a preclinical study, efficacy of trastuzumab, lapatinib, and NVP-BEZ235 (dactolisib) combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirall… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PIK3CA H1047R6 | ||||||||
| Dactolisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 4 | accepted | EID6206This preclinical study tested the sensitivity of HER2-positive breast cancer cell line BT-474 (heterozygous for PIK3CA K111N) retrovirally transduced with PIK3CA H1047R to NVP-BEZ235 (dactolisib; a du… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8182In a preclinical study, efficacy of trastuzumab and NVP-BEZ235 (dactolisib) combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirally induced PI… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6202This preclinical study tested, in vitro, the resistance to lapatinib (an anti-HER2 drug) of HER2-positive breast cancer cell lines (BT474 and SKBR3) retrovirally transduced with H1047R. The study foun… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 3 | submitted | EID6205This preclinical study tested the sensitivity to lapatinib and NVP-BEZ235 (dactolisib; a dual PI3K/mTOR inhibitor) of a HER2-positive breast cancer cell line (BT474) retrovirally transduced with PIK3C… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID6204In a preclinical study, efficacy of lapatinib and trastuzumab was evaluated in vitro against HER2 amplified breast cancer cell line BT474 (heterozygous for PIK3CA K111N) retrovirally transduced with P… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6203This preclinical study tested the effect of trastuzumab (an anti-HER2 drug) on HER2-positive breast cancer cell lines (BT474 and SKBR3) retrovirally transduced with H1047R. The study found that the H1… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PIK3CA K111N1 | ||||||||
| Dactolisib + Lapatinib + TrastuzumabSubstitutes | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 2 | accepted | EID8183The BT-474 HER2 positive human breast cancer cell line, which is heterozygous for the PIK3CA K111N mutation, demonstrated strongly reduced colony formation when treated with lapatinib, trastuzumab or … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PIK3CA K111N + PTEN UnderexpressionPIK3CAPTEN7 | ||||||||
| Dactolisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8276In a preclinical study, efficacy of dactolisib monotherapy was evaluated in vitro against HER2 amplified human breast cancer cell line BT474 (heterozygous for PIK3CA K111N) with shRNA-induced PTEN exp… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8283In a preclinical study, efficacy of NVP-BEZ235 (dactolisib) and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with shRNA-induced PTEN expr… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID8275In a preclinical study, efficacy of trastuzumab monotherapy was evaluated in vitro against HER2 amplified human breast cancer cell line BT474 (heterozygous for PIK3CA K111N) with shRNA-induced PTEN ex… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 2 | accepted | EID8278In a preclinical study, efficacy of NVP-BEZ235 (dactolisib; a dual PI3K/mTOR inhibitor) and lapatinib combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 (h… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8277In a preclinical study, efficacy of lapatinib and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with shRNA-induced PTEN expression loss. A… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8274In a preclinical study, efficacy of trastuzumab monotherapy was evaluated in vitro against HER2 amplified human breast cancer cell line BT474 (heterozygous for PIK3CA K111N) with shRNA-induced PTEN ex… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 2 | accepted | EID8279In a preclinical study, efficacy of NVP-BEZ235 (dactolisib; a dual PI3K/mTOR inhibitor) and trastuzumab combination therapy was evaluated in vitro against HER2 amplified human breast cancer cell line … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PIK3CA Overexpression4 | ||||||||
| Dactolisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8269In a preclinical study, efficacy of NVP-BEZ235 (dactolisib) monotherapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirally induced PIK3CA amplification. Auth… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8268In a preclinical study, efficacy of lapatinib monotherapy was evaluated in vitro against HER2 amplified breast cancer cell lines (BT474 and SKBR3) with retrovirally induced PIK3CA expression. Authors … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8270In a preclinical study, efficacy of lapatinib and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell lines (BT474 and SKBR3) with retrovirally induced PIK… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8267HER2-positive breast cancer cell lines (BT-474 and SKBR3) were retrovirally transduced with wildtype PIK3CA and treated with trastuzumab. PIK3CA overexpression diminished the growth inhibitory effects… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PTEN Loss1 | ||||||||
| Dactolisib + Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8280In a preclinical study, efficacy of NVP-BEZ235 (dactolisib), lapatinib, and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with shRNA-induc… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |