Gene

PIK3CA

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

Explore in graph →CI-GENE-00019747HGNC:8975 ENSG00000121879 NCBI 5290 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (298)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 51–100 of 298 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
PIK3CA E542Q1
PI103	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted

Cohorts

Alteration frequency by cohort (200)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved200 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Metastatic Breast Cancer (INSERM, PLoS Med 2016) brca_igr_2015	Invasive Breast Carcinoma	Ssm	66

Literature

Linked publications (65)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 65 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer.
· N Engl J Med · 2019 · PMID 31091374 · validated civic_curation pubmed
Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.
· N Engl J Med · 2023 · PMID 37256976 · validated civic_curation pubmed
US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Locally Advanced or Metastatic Breast Cancer.
· J Clin Oncol · 2025 · PMID 40845250 · validated civic_curation pubmed
PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis.

PIK3CA E545A2
Capivasertib + FulvestrantCombination	HER2 Negative Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	2	submitted	EID12185 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic
PI103	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID2052 In H460, a gefitinib-resistant NSCLC cell line that harbors PIK3CA mutations, the dual PI3Kalpha/mTOR inhibitor PI103 reduced cell growth and increased the expression of the tumor suppressor p53 compa… (full text at CIViC) PMID 19513541 · Zou et al., 2009 · Open in CIViC	civic

PIK3CA E545A2

Capivasertib + FulvestrantCombination

HER2 Negative Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

submitted

EID12185

In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC)

PMID 37256976 · Turner et al., 2023 · Open in CIViC

PIK3CA E545G7
Aspirin	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	—	rejected	EID2069 In a study of 413 patients with colorectal cancer who were taking aspirin since diagnosis, the frequency of PIK3CA mutations was 17% (70/413). In 530 patients with colorectal cancer not using aspirin,… (full text at CIViC) PMID 23094721 · Liao et al., 2012 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	—	submitted	EID2070 Phosphatidylinositol 3-kinase (PIK3CA) is composed of an 85kDa regulatory subunit and a 110kDa (p110alpha) catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which u… (full text at CIViC) PMID 9742087 · Klippel et al., 1998 · Open in CIViC	civic
Capivasertib + FulvestrantCombination	HER2 Negative Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	2	submitted	EID12189 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	rejected	EID3723 In a retrospective study of 168 chemotherapy-refractory metastatic colorectal cancer patients, patients with a PIK3CA mutation (n=26) treated with cetuximab in combination with standard chemotherapy, … (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
PI103	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID2063 In H460, a gefitinib-resistant NSCLC cell line that harbors PIK3CA mutations, the dual PI3Kalpha/mTOR inhibitor PI103 reduced cell growth and increased the expression of the tumor suppressor p53 compa… (full text at CIViC) PMID 19513541 · Zou et al., 2009 · Open in CIViC	civic
Trastuzumab	Malignant Breast Neoplasm	Predictive	C	Supports Resistance	—	submitted	EID2060 In HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation was associated with an increased risk of progression (HR:2.50, 95% CI:1.35-4.… (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	2	accepted	EID3724 An in vitro study of M229 (a human melanoma cell line) endogenously expressing wildtype PIK3CA and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that cells virally induced to stably o… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

PIK3CA E545K32
(prognostic)	Rectal CarcinomaALIAS	Prognostic	B	Supports Poor Outcome	2	accepted	EID2106 This study examined outcomes of 240 rectum cancer patients treated with total mesorectal excision therapy. Tumor samples were obtained at the time of surgery and genotyped for PIK3CA exon 10 and 21 mu… (full text at CIViC) PMID 19903786 · He et al., 2009 · Open in CIViC	civic
Akt Inhibitor MK2206 + PictilisibSubstitutes	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	3	accepted	EID710 PIK3CA E545K mutation increased sensitivity to AKT inhibitor MK-2206 and PI3K inhibitor GDC-0941 in a breast cancer cell line model. PMID 23888070 · Beaver et al., 2013 · Open in CIViC	civic
Apitolisib	Malignant NeoplasmALIAS	Predictive	C	Supports Sensitivity Response	1	accepted	EID1550 Phase 1 study with the dual PI3K/mTOR inhibitor apitolisib. 120 patients were treated at doses between 2 and 70mg. Of 45 evaluable patients receiving 40mg, two patients with E545K PIK3CA mutation (one… (full text at CIViC) PMID 26787751 · Dolly et al., 2016 · Open in CIViC	civic
Aspirin	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	—	submitted	EID2039 Phosphatidylinositol 3-kinase (PIK3CA) is composed of an 85kDa regulatory subunit and a 110kDa (p110alpha) catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which u… (full text at CIViC) PMID 9742087 · Klippel et al., 1998 · Open in CIViC	civic
Capivasertib + FulvestrantCombination	HER2 Negative Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	2	submitted	EID12188 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	—	submitted	EID3720 In metastatic colorectal cancer, the objective tumor response rate to the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab or panitumumab was lower in patients with PIK3CA … (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Does Not Support Resistance	3	accepted	EID2217 This was a retrospective study of 691 cetuximab treated patients with metastatic, chemotherapy refractory colorectal cancer. Of those, 16 patients harbored PIK3CA E545K (exon 10), were wt for BRAF, NR… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	rejected	EID3721 In colorectal cancer patients treated with salvage cetuximab therapy in combination with chemotherapy, PIK3CA mutations were associated with reduced progression-free survival (2.5mo vs. 3.9mo, HR:2.1,… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
Cetuximab + PanitumumabSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID387 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS PIK3CA and PTEN we… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
Cisplatin	Malignant Cervical Neoplasm	Predictive	D	Supports Resistance	3	accepted	EID2985 Authors tested various cervical cancer cell lines (CaSki, SiHa and HeLa) for their responses to cisplatin, radiation therapy, and GDC-0941. CaSki cells that are heterozygous for the PIK3CA-E545K mutat… (full text at CIViC) PMID 27489350 · Arjumand et al., 2016 · Open in CIViC	civic
Cisplatin + Ionizing RadiotherapySequential	Malignant Cervical Neoplasm	Predictive	D	Supports Resistance	3	accepted	EID8112 Cervical cancer cell lines were treated with 1uM cisplatin followed by 1-6Gy ionizing radiation (IR). CaSki cells with PIK3CA E545K mutation show resistance to cisplatin plus IR when compared with HeL… (full text at CIViC) PMID 27489350 · Arjumand et al., 2016 · Open in CIViC	civic
Dactolisib	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Does Not Support Resistance	3	accepted	EID6213 This 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	EID8180 In 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
Gefitinib	Lung Adenocarcinoma	Predictive	D	Supports Resistance	2	accepted	EID1171 HCC827 cell lines harboring activated PI3K (HCC827 p110α E545K cells) were more resistant to gefitinib in vitro (IC50, 1 μM) compared with those harboring GFP alone (IC50, 0.01 μM). The presence of p1… (full text at CIViC) PMID 16906227 · Engelman et al., 2006 · Open in CIViC	civic
Erlotinib + GefitinibSubstitutes	Lung Adenocarcinoma	Predictive	C	Supports Resistance	2	accepted	EID1670 48 tumor samples from 41 patients with EGFR mutant lung adenocarcinoma that were resistant to tyrosine kinase inhibition underwent next generation sequencing (AmpliSeq Cancer Hotspot Panel (v2) failed… (full text at CIViC) PMID 27304188 · Belchis et al., 2016 · Open in CIViC	civic
Lapatinib	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Resistance	3	accepted	EID6207 This 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	EID6212 This 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	EID6211 In 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
Cetuximab + PanitumumabSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Does Not Support Resistance	2	accepted	EID2037 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). PIK3CA E545K was the on… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
PI-103	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	1	accepted	EID8008 As part of a preclinical study, the efficacy of PI-103 was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized as less than and more than an IC50 of 1umol/L, … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
PI103	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID2040 H460, a gefitinib-resistant NSCLC cell line harboring PIK3CA E545K (a PIK3CA activating mutation), was used to test the anti-tumor effects of PI103. Without treatment, H460 cells expressed high levels… (full text at CIViC) PMID 19513541 · Zou et al., 2009 · Open in CIViC	civic
PI3Ka/Di	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	1	accepted	EID8017 As part of a preclinical study, the efficacy of PI3KA/Di—a selective inhibitor for the α (IC50 for p100α: 3nM) and δ (IC50 for p100δ: 20nM) subunits of class I PI3K—was evaluated for several cell line… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
〃	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	1	accepted	EID8018 As part of a preclinical study, the efficacy of PI3KA/Di—a selective inhibitor for the α (IC50 for p100α: 3nM) and δ (IC50 for p100δ: 20nM) subunits of class I PI3K—was evaluated for several cell line… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
Pictilisib	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	4	accepted	EID2062 This preclinical study tested the efficacy on several breast cancer cell lines of GDC-0941 (pictilisib), a selective inhibitor of all four isoforms of class I PI3-kinases at a range of IC50 values. Se… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
〃	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	2	accepted	EID2034 This preclinical study tested the efficacy on several breast cancer cell lines of GDC-0941 (pictilisib), a selective inhibitor of all four isoforms of class I PI3-kinases over a range of IC50 values. … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
Cisplatin + PictilisibCombination	Cervical CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID2984 CaSki cells that are heterozygous for the PIK3CA-E545K mutation are more resistant to cisplatin or cisplatin plus radiation than either HeLa or SiHa cells that express only wild-type PIK3CA. Similarly… (full text at CIViC) PMID 27489350 · Arjumand et al., 2016 · Open in CIViC	civic
Trastuzumab	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Resistance	3	accepted	EID6209 This 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
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Resistance	2	accepted	EID1453 PI3K mutant E545K was overexpressed in the trastuzumab sensitive HER2 BT474 breast cancer cell line, and significant resistance to trastuzumab was induced in comparison to control cells. PMID 18829560 · Serra et al., 2008 · Open in CIViC	civic
〃	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Resistance	2	accepted	EID8547 As part of a pre-clinical experiment, the efficacy of trastuzumab was evaluated against various HER2 positive cell lines. MCF7-neo/HER2 cell line harboring PIK3CA E545K was associated with resistance … (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC	civic
Dactolisib + Lapatinib + TrastuzumabCombination	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Sensitivity Response	2	submitted	EID8181 In 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
Trastuzumab Emtansine	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Does Not Support Resistance	3	accepted	EID2036 As part of a pre-clinical experiment, the efficacy of ado-trastuzumab emtansine (T-DM1) was compared to that of trastuzumab against various HER2 positive cell lines. MCF7-neo/HER2 cell line harboring … (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	2	accepted	EID3722 An in vitro study of M229 (a human melanoma cell line) endogenously expressing wildtype PIK3CA and BRAF V600E (a known BRAF inhibitor sensitizing mutation) used PIK3CA E545K as a positive control for … (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic