Variant · Snv

PIK3CA E545K

CI-VAR-00000778Explore in graph →NP_006209.2:p.Glu545LysNM_006218.3:c.1633G>AClinVar 13655 CIViC 104 rs104886003

Curated evidence

Evidence by cancer (38 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–38 of 38 evidence items across 13 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Cervical Carcinoma1
PIK3CA E545K	Cisplatin + PictilisibCombination	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
HER2-Positive Breast Carcinoma12
PIK3CA E545K	Dactolisib	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…

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
13655	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	OVARIAN CANCER, EPITHELIAL, SOMATIC; Breast adenocarcinoma; Carcinoma of colon; Seborrheic keratosis; Non-small cell lung carcinoma; Megalencephaly-capillary malformation-polymicrogyria syndrome; Sarcoma; Ovarian neoplasm; Abnormal cardiovascular system morphology; Gallbladder cancer; Segmental undergrowth associated with lymphatic malformation; CLOVES syndrome; Cerebrofacial Vascular Metameric Syndrome (CVMS); Eccrine angiomatous hamartoma; PIK3CA related overgrowth syndrome; Gastric cancer; HEMIFACIAL MYOHYPERPLASIA, SOMATIC; Angioosteohypertrophic syndrome; Rare venous malformation; Rare combined vascular malformation; Neoplasm; PIK3CA overgrowth syndrome; PIK3CA-related disorder; IDH-wildtype glioblastoma; Rosette-forming glioneuronal tumor; Medulloblastoma WNT activated; Adenocarcinoma of the large intestine; Lymphatic malformation; Cervical squamous cell carcinoma; Embryonal rhabdomyosarcoma; Congenital fibrosarcoma; Cerebral cavernous malformation

Lung Adenocarcinoma3
PIK3CA E545K	Gefitinib	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
PIK3CA E545K	Erlotinib + GefitinibSubstitutes	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
PIK3CA E545K AND MET Exon 14 Skipping Mutation	Crizotinib + PictilisibCombination	Predictive	D	Supports Sensitivity Response	3	submitted	EID11376 Lung adenocarcinoma cell lines with MET exon 14 skipping mutation and PIK3CA mutation (H596) were tested with GDC0941 (pictilisib) alone and with crizotinib. Analysis shows a statistically significant… (full text at CIViC) PMID 26215952 · Liu et al., 2016 · Open in CIViC	civic

Lung Adenocarcinoma3

PIK3CA E545K

Gefitinib

Predictive

Supports Resistance

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

Malignant Breast Neoplasm7
PIK3CA E542K OR PIK3CA E545K OR PIK3CA H1047R	FAC Regimen + FEC RegimenSubstitutes	Predictive	B	Does Not Support Resistance	3	accepted	EID6191 This study of 140 patients with stage II-III breast cancer assessed the response of patients with PIK3CA mutations to 6 months of preoperative chemotherapy. Exons 1, 9, and 20 of PIK3CA were screened… (full text at CIViC) PMID 18371219 · Liedtke et al., 2008 · Open in CIViC	civic
PIK3CA E545K	Akt Inhibitor MK2206 + PictilisibSubstitutes	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
PIK3CA E545K	PI-103	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
PIK3CA E545K	PI3Ka/Di	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
PIK3CA E545K	Pictilisib	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
PIK3CA E545K OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545D	Alpelisib + FulvestrantCombination	Predictive	A	Supports Sensitivity Response	4	accepted	EID7468 In a phase 3 trial, 572 patients with hormone receptor positive, HER2 receptor negative advanced breast cancer who previously received endocrine therapy were allocated to alpelisib plus fulvestrant or… (full text at CIViC) PMID 31091374 · André et al., 2019 · Open in CIViC	civic
PIK3CA E545K OR PIK3CA E545Q OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545V OR PIK3CA E545D OR PIK3CA E545L OR PIK3CA E545R	Fulvestrant + Inavolisib + PalbociclibCombination	Predictive	A	Supports Sensitivity Response	3	accepted	EID12534 The phase III INAVO120 trial (NCT04191499) in 325 patients with endocrine-resistant, PIK3CA-mutated HR⁺/HER2⁻ locally advanced or metastatic breast cancer evaluated inavolisib plus palbociclib and ful… (full text at CIViC) PMID 40845250 · Wedam et al., 2025 · Open in CIViC	civic

Malignant Cervical Neoplasm2
PIK3CA E545K	Cisplatin	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
PIK3CA E545K	Cisplatin + Ionizing RadiotherapySequential	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

Malignant Colorectal Neoplasm6
PIK3CA E545K	Aspirin	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
PIK3CA E545K	Cetuximab	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
PIK3CA E545K	Cetuximab	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
PIK3CA E545K	Cetuximab	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
PIK3CA E545K	Cetuximab + PanitumumabSubstitutes	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
PIK3CA E545K	Cetuximab + PanitumumabSubstitutes	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