Subtype
Malignant Neoplasm of Unknown Primary
CI-CAN-00001150CUPExplore in graph →
- NCIt
- C8566
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Subtype
CI-CAN-00001150CUPExplore in graph →
Variants & evidence
1,035 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| BRAF Mutation + KRAS Mutation + NRAS MutationKRASNRASBRAF1 | ||||||||
| (prognostic) | Colorectal Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID11061The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| NRAS Q613 | ||||||||
| (prognostic) | Thyroid Gland Follicular CarcinomaALIAS | Prognostic | B | Supports N/A | 3 | accepted | EID497In patients with follicular thyroid carcinoma, those with mutations in NRAS at codon 61 did not have significantly different overall survival than patients with wild-type NRAS (p=0.36). PMID 22650231 · Fukahori et al., 2012 · Open in CIViC | civic |
| 〃 | Thyroid Gland Follicular CarcinomaALIAS | Prognostic | B | Does Not Support Poor Outcome | 2 | accepted | EID6959Follicular thyroid cancers harboring RAS mutations have limited aggressiveness in the absence of TERT mutations. 2/2 follicular thyroid cancer patients with co-mutations in NRAS (10 Q61R and 1 Q61K) o… (full text at CIViC) PMID 25448848 · Muzza et al., 2015 · Open in CIViC | civic |
| 〃 | Thyroid Gland Follicular CarcinomaALIAS | |||||||
| NRG1 Expression1 | ||||||||
| Lapatinib | Head and Neck Squamous Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID776In non-HER2 amplified cell lines, sensitivity to HER2 kinase inhibitor lapatinib was found mainly in cell-lines with elevated NRG1 expression and HER3 activation. This aberration was mainly identified… (full text at CIViC) PMID 21840482 · Wilson et al., 2011 · Open in CIViC | civic |
| RASGRF1 Fusion1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID1071625 tumors from individuals with lung adca who have <= 10 pack-year smoking history underwent whole exome sequencing and RNA-seq. 5 tumors did not identify an established oncogenic driver. In one (tumo… (full text at CIViC) PMID 35247929 · Hunihan et al., 2022 · Open in CIViC | civic |
| PALB2 Mutation1 | ||||||||
| Talazoparib | Pancreatic Ductal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID10835A patient with pancreatic ductal adenocarcinoma (PDAC) and a somatic PALB2 mutation (NM_024675.4: c.3350+1G>T) experienced disease progression after 10 cycles of FOFIRINOX and 2 cycles of gemcitabine.… (full text at CIViC) PMID 36119518 · Kachmazov et al., 2022 · Open in CIViC | civic |
| PAPPA2 Y1520X1 | ||||||||
| Pembrolizumab | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | — | submitted | EID4774In a retrospective study of 34 non-small cell lung cancer patients, a lung adenocarcinoma patient with PAPPA2 Y1520* nonsense mutation, treated with pembrolizumab monotherapy, was associated with a 4 … (full text at CIViC) PMID 25765070 · Rizvi et al., 2015 · Open in CIViC | civic |
| PPARG Fusion1 | ||||||||
| (diagnostic) | Thyroid Gland Follicular CarcinomaALIAS | Diagnostic | B | Supports Positive | 3 | accepted | EID498PAX8–PPARG gene fusions were found in 12/33 follicular thyroid carcinoma tumor samples, but were rarely found in thyroid Hürthle cell tumors. PMID 12727991 · Nikiforova et al., 2003 · Open in CIViC | civic |
| PBK NUCLEAR EXPRESSION1 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 2 | accepted | EID1052Microarray expression data from 48 patients with gastric adenocarcinoma were analyzed for genes differentially expressed with regard to overall survival. Upregulation of proteasome subunit beta type 8… (full text at CIViC) PMID 26894977 · Kwon et al., 2016 · Open in CIViC | civic |
| PBLD Underexpression1 | ||||||||
| (prognostic) | Hepatocellular Carcinoma | Prognostic | D | Supports Poor Outcome | 4 | submitted | EID6364The frequent deletion of PBLD in HCC tissues is an independent predictor of poor prognosis for patients with HCC. Elevated PBLD expression has been show to reduce the growth and spread of HCC. PMID 26594798 · Li et al., 2016 · Open in CIViC | civic |
| PBRM1 Loss-of-function4 | ||||||||
| Atezolizumab + DurvalumabSubstitutes | Renal Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7537Among 35 patients with clear cell RCC, loss-of-function mutation of PBRM1 were correlated with response to anti-PD-1 monotherapy (P = 0.012). It was confirmed in an independent validation cohort of 63… (full text at CIViC) PMID 29301960 · Miao et al., 2018 · Open in CIViC | civic |
| Ipilimumab | Renal Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7301Among 35 patients with clear cell RCC, loss-of-function mutation of PBRM1 were correlated with response to anti-PD-1 monotherapy (P = 0.012). It was confirmed in an independent validation cohort of 6… (full text at CIViC) PMID 29301960 · Miao et al., 2018 · Open in CIViC | civic |
| Nivolumab | ||||||||
| PBRM1 Mutation4 | ||||||||
| (prognostic) | Clear Cell Renal Cell Carcinoma | Prognostic | B | Supports N/A | 3 | accepted | EID420In renal clear cell carcinoma, patients with PBRM1 mutations did not have a significantly different cancer specific survival. PMID 23620406 · Hakimi et al., 2013 · Open in CIViC | civic |
| 〃 | Renal Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | accepted | EID499In patients with sporatic clear cell renal cell carcinoma, those with mutations in PBRM1 had better overall survival than patients with BAP1 mutations. PMID 23333114 · Kapur et al., 2013 · Open in CIViC | civic |
| Anti-PD-L1 Monoclonal Antibody + CTLA-4 InhibitorSubstitutes | Clear Cell Renal Cell Carcinoma | Predictive | B | Supports | ||||
| PDGFRA Amplification1 | ||||||||
| Imatinib + SunitinibSubstitutes | Lung Squamous Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID7989Cell line NCI-H1703 is PDGFRA amplified and KIT wild-type. NCI-H1703 was treated with a PDGFRA inhibitor, imatinib or sunitinib. The IC50 of imatinib or sunitinib was lower in PDGFRA amplified NCI-H… (full text at CIViC) PMID 19755855 · Ramos et al., 2009 · Open in CIViC | civic |
| PIK3CA Activation mutation1 | ||||||||
| (oncogenic) | Ovarian Clear Cell Adenocarcinoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13136Ovarian clear cell carcinoma is an aggressive and relatively chemotherapy-resistant form of ovarian cancer with a molecular landscape distinct from that of the more common epithelial subtypes. Earlier… (full text at CIViC) PMID 19349352 · Kuo et al., 2009 · Open in CIViC | civic |
| PIK3CA Amplification6 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID504In patients with gastric cancer, those with amplification of PIK3CA had shorter overall survival than those without amplification. PMID 22292935 · Shi et al., 2012 · Open in CIViC | civic |
| Aspirin + Ibuprofen + SulindacSubstitutes | Head and Neck Squamous Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7186In this retrospective study, the impact of nonsteroidal anti-inflammatory drugs (NSAID) on survival in PIK3CA-altered HNSCC patients (N=266) was assessed. 37 of 266 (14%) patients harbored a mutation,… (full text at CIViC) PMID 30683736 · Hedberg et al., 2019 · Open in CIViC | civic |
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | |||||||
| PIK3CA C420R3 | ||||||||
| Pictilisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2078This preclinical study tested the efficacy on several HER2 amplified breast cancer cell lines of GDC-0941 (pictilisib), a selective inhibitor of all four isoforms of class I PI3-kinases at a range of … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8549As part of a pre-clinical experiment, the efficacy of trastuzumab was evaluated against various HER2 positive cell lines. EFM-192A cell line expressing PIK3CA C420R was associated with resistance to t… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| Trastuzumab Emtansine | HER2-Positive Breast Carcinoma | |||||||
| PIK3CA E542K4 | ||||||||
| Apitolisib | Head and Neck Squamous Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1549Phase 1 study with the dual PI3K/mTOR inhibitor apitolisib. 120 patients were treated at doses between 2 and 70mg. Of the 14 evaluable patients with PIK3CA mutations total, there were 3 PRs (1 confirm… (full text at CIViC) PMID 26787751 · Dolly et al., 2016 · Open in CIViC | civic |
| PI-103 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID2058As part of a preclinical study, the efficacy of PI-103 (a dual inhibitor of MTOR and Class IA PI3Ks) was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized a… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC | civic |
| PI3Ka/Di | HER2-Positive Breast CarcinomaALIAS | |||||||
| PIK3CA E545K14 | ||||||||
| 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 |
| Gefitinib | ||||||||
| MET Exon 14 Skipping Mutation + PIK3CA E545KMETPIK3CA1 | ||||||||
| Crizotinib + PictilisibCombination | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11376Lung 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 |
| PIK3CA H1047R1 | ||||||||
| Capivasertib + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1506The HER2 breast cancer cell line KPL4 with PIK3CA H1047R shows sub-optimal responses to trastuzumab and lapatinib, and was used to establish mouse xenografts. Treatment of mice with monotherapy of AZD… (full text at CIViC) PMID 22294718 · Davies et al., 2012 · Open in CIViC | civic |
Data updated 1 hour agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Prognostic |
| B |
| Supports Poor Outcome |
| 2 |
| submitted |
EID7104Retrospective analysis of thyroid carcinoma patients from a single institution identified 33/58 patients with follicular carcinomas had any RAS mutations (NRAS, KRAS, or HRAS at codons 12 or 61), 22 o… (full text at CIViC) PMID 22650231 · Fukahori et al., 2012 · Open in CIViC |
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| Renal Cell CarcinomaCURATED_BROADER |
| Predictive |
| B |
| Supports Sensitivity Response |
| 4 |
| submitted |
EID7584In post hoc analysis in phase 3 trial, which compared nivolumab and everolimus in patients with clear cell renal cell carcinoma who received prior antiangiogenic therapy, PBRM1 mutations were identifi… (full text at CIViC) PMID 31486842 · Braun et al., 2019 · Open in CIViC |
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| Nivolumab + PembrolizumabSubstitutes | Renal Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7536Among 35 patients with clear cell RCC, loss-of-function mutation of PBRM1 were correlated with response to anti-PD-1 monotherapy (P = 0.012). It was confirmed in an independent validation cohort of 63… (full text at CIViC) PMID 29301960 · Miao et al., 2018 · Open in CIViC | civic |
| 4 |
| submitted |
EID7247Clinical benefit to immune checkpoint blockade was associated with loss-of-function mutations in the PBRM1 gene (P = 0.012), which encodes a subunit of the PBAF switch-sucrose nonfermentable (SWI/SNF)… (full text at CIViC) PMID 29301960 · Miao et al., 2018 · Open in CIViC |
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| Everolimus + SunitinibSequential | Renal Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID5996This study evaluated the relationship between tumor mutations and treatment outcomes in the RECORD-3 clinical trial. With first-line everolimus, PBRM1 and BAP1 mutations were associated with longer (m… (full text at CIViC) PMID 27751729 · Hsieh et al., 2017 · Open in CIViC | civic |
| 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 |
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| 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 |
| Taselisib | Head and Neck Squamous Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID1464The HNSCC cell line LB771 with PIK3CA amplification was shown to have low antiproliferative IC50 for the p110beta-sparing PI3K inhibitor taselisib. Under increasing taselisib concentrations, reduction… (full text at CIViC) PMID 26589432 · Zumsteg et al., 2016 · Open in CIViC | civic |
| Predictive |
| D |
| Does Not Support Resistance |
| 3 |
| accepted |
EID2346As 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. EFM-192A cell line expressing PIK3… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC |
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| D |
| Supports Sensitivity Response |
| 1 |
| accepted |
EID8013As part of a preclinical study, the efficacy of PI3KA/Di—a selective inhibitor for the α and δ subunits of class I PI3K—was evaluated for several cell lines of breast cancer. Sensitivity and resistanc… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC |
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| Pictilisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID2022This 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 |
| Lung Adenocarcinoma |
| Predictive |
| D |
| Supports Resistance |
| 2 |
| accepted |
EID1171HCC827 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 |
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| Erlotinib + GefitinibSubstitutes | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 2 | accepted | EID167048 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 | 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 |
| PI3Ka/Di | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID8017As 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 | EID2062This 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 |
| 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 |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID1453PI3K 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 | EID8547As 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 | 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 |
| Trastuzumab Emtansine | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 3 | accepted | EID2036As 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 |