Histology
Carcinoma of Unknown Primary
CI-CAN-00002109Explore in graph →
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Histology
CI-CAN-00002109Explore in graph →
Variants & evidence
1,033 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 |
|---|---|---|---|---|---|---|---|---|
| RET M918T + RET V804M2 | ||||||||
| Selpercatinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID6950After progressing on 6 multi-kinase inhibitor (MKI) regimens (including sorafenib , vandetanib, cabozantinib, MGCD-516, RXDX-105, and vandetanib plus everolimus ), a metastatic medullary thyroid cance… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | rejected | EID11307After progressing on 6 multi-kinase inhibitor (MKI) regimens (including sorafenib , vandetanib, cabozantinib, MGCD-516, RXDX-105, and vandetanib plus everolimus ), a metastatic medullary thyroid cance… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC | civic |
| RET Mutation5 | ||||||||
| (prognostic) | Thyroid Gland Medullary CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID74In a study of 100 patients with sporadic medullary thyroid carcinoma (MTC), RET gene exons 10-11 and 13-16 were analyzed with tumor and matched normal samples. A somatic RET mutation was identified in… (full text at CIViC) PMID 18073307 · Elisei et al., 2008 · Open in CIViC | civic |
| Cabozantinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID8984In this retrospective analysis of a phase 3 trial of cabozantinib or placebo in 330 patients. Among those, 51.2% were RET mutation-positive (38.2% with RET M918T), 34.8% were RET mutation-unknown, and… (full text at CIViC) PMID 27525386 · Sherman et al., 2016 · Open in CIViC | civic |
| Selpercatinib | Thyroid Gland Medullary Carcinoma | |||||||
| RET Overexpression2 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID7056ASCL1 and RET mRNA levels were examined by microarray analysis in lung cancer samples. High expression of RET (RET-high) correlated with shorter overall survival compared to the RET-low group in patie… (full text at CIViC) PMID 24037524 · Kosari et al., 2014 · Open in CIViC | civic |
| Sunitinib | Papillary Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1518A 78-year-old man presented with oral papillary adenocarcinoma and lung metastases that were refractory to standard treatment. Tumor sequencing showed increased MAPK activity due to RET over-expressi… (full text at CIViC) PMID 20696054 · Jones et al., 2010 · Open in CIViC | civic |
| RET V804M2 | ||||||||
| Selpercatinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID6951A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid r… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7068In this phase 1 trial, 57 patients were treated with the selective RET Inhibitor selpercatinib (LOXO-292). A 57-year-old male with a hereditary RET V804M gatekeeper mutation treated with 3 prior multi… (full text at CIViC) | civic |
| RET Y806C1 | ||||||||
| Pralsetinib + SelpercatinibSubstitutes | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Resistance | 3 | submitted | EID8920Cell-free DNA was analysed in a patient with RET-mutant (M918T and V804M) medullary thyroid cancer and another patient with CCDC6-RET fusion positive non-small cell lung cancer who had developed acqui… (full text at CIViC) PMID 33161056 · Subbiah et al., 2021 · Open in CIViC | civic |
| RET Y806N1 | ||||||||
| Pralsetinib + SelpercatinibSubstitutes | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Resistance | 3 | submitted | EID8921Cell-free DNA was analysed in a patient with RET-mutant (M918T and V804M) medullary thyroid cancer and another patient with CCDC6-RET fusion positive non-small cell lung cancer who had developed acqui… (full text at CIViC) PMID 33161056 · Subbiah et al., 2021 · Open in CIViC | civic |
| RICTOR Amplification4 | ||||||||
| Onatasertib + SapanisertibSubstitutes | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1440Study describes an 18 year old never smoker patient presenting with lung adenocarcinoma. A genomic profiling assay (FoundationOne) revealed a 7-copy amplification of RICTOR as the only somatic alterat… (full text at CIViC) PMID 26370156 · Cheng et al., 2015 · Open in CIViC | civic |
| Vistusertib | Lung Small Cell Carcinoma | Predictive | C | Does Not Support Sensitivity Response | 3 | accepted | EID7449In a phase 2 basket trial, patients with small-cell lung carcinoma (SLC) who failed platinum-based chemotherapy and harbored RICTOR amplification were treated with mTOR 1/2 inhibitor vistusertib (AZD2… (full text at CIViC) | civic |
| 〃 | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | ||||
| RIT1 A77P1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9830RIT1 mutations were identified in lung adenocarcinoma tumors lacking typical driver gene mutations. RIT1 A77P was expressed in NIH3T3 cells and induced colony formation in soft agar. Similarly, RIT1 A… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| RIT1 A77S1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9831RIT1 mutations were identified in lung adenocarcinoma tumors lacking typical driver gene mutations. RIT1 A77S was expressed in NIH3T3 cells and induced colony formation in soft agar. Similarly, RIT1 A… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| RIT1 F82L1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9834RIT1 mutations were identified in lung adenocarcinoma tumors lacking typical driver gene mutations. RIT1 F82L was expressed in NIH3T3 cells and induced colony formation in soft agar. Similarly, RIT1 F… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| RIT1 M90I1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9825RIT1 mutations were identified in lung adenocarcinoma tumors lacking typical driver gene mutations. RIT1 M90I was expressed in NIH3T3 cells and induced colony formation in soft agar. Similarly, RIT1 M… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| RIT1 Mutation1 | ||||||||
| Pictilisib + SelumetinibSubstitutes | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID742RIT1 mutations were identified in approx. 2% of lung adenocarcinomas (5/87 in the "oncogene negative" samples of TCGA - no RIT1 mutations were observed in 143 samples with a known driver mutation). GD… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| NF1 Mutation + RIT1 MutationRIT1NF11 | ||||||||
| (diagnostic) | Lung Adenocarcinoma | Diagnostic | B | Supports Positive | 5 | submitted | EID11373This study contained 230 patients with untreated lung adenocarcinoma. Whole-exome sequencing of tumor cells yielded that RTK/RAS/RAF based mutations to be 62%. However, analysis shows that NF1 mutatio… (full text at CIViC) PMID 25079552 · 2014, Nature · Open in CIViC | civic |
| RIT1 Q40L1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Does Not Support Oncogenicity | 3 | submitted | EID9829RIT1 mutations were identified in lung adenocarcinoma tumors lacking typical driver gene mutations. RIT1 Q40L was expressed in NIH3T3 cells and did not induce colony formation in soft agar greater tha… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| RIT1 Q79L1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9827RIT1 mutations were identified in lung adenocarcinoma tumors lacking typical driver gene mutations. RIT1 Q79L, a known activating mutation, was expressed in NIH3T3 cells and induced colony formation i… (full text at CIViC) PMID 24469055 · Berger et al., 2014 · Open in CIViC | civic |
| ROS1 D2033N1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | — | submitted | EID4770In a metastatic lung adenocarcinoma patient with a CD74-ROS1 gene fusion (a known sensitizing alteration to crizotinib) and a D2033N mutation in the ROS1 portion of the CD74-ROS1 gene fusion, D2033N w… (full text at CIViC) PMID 26673800 · Drilon et al., 2016 · Open in CIViC | civic |
| ROS1 G2032R1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 1 | accepted | EID2934Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. A biopsy of a resistan… (full text at CIViC) PMID 23724914 · Awad et al., 2013 · Open in CIViC | civic |
| ROS1 Fusion + ROS1 G2032R1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 4 | accepted | EID1100Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. An acquired G2032R mut… (full text at CIViC) PMID 23724914 · Awad et al., 2013 · Open in CIViC | civic |
| ROS1 G2032R + ROS1 Fusion1 | ||||||||
| DS-6501b | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID7538In preclinical models, DS-6051b inhibited tumour growth and phospho-ROS1 levels in CD74-ROS1 G2032R mutant Ba/F3 cells. Similar results were seen in the crizotinib-resistant patient derived MGH047-4 c… (full text at CIViC) PMID 31399568 · Katayama et al., 2019 · Open in CIViC | civic |
| RPS6 PHOSPHORYLATION1 | ||||||||
| Everolimus | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID93054 patients with advanced gastric cancer were treated with everolimus. Two patient responsed and potential biomarkers were explored. High pre-treatment expression of phosphorylated RPS6 (pS6; at Ser24… (full text at CIViC) PMID 22343617 · Yoon et al., 2012 · Open in CIViC | civic |
| SCN8A Q225X1 | ||||||||
| Pembrolizumab | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | — | submitted | EID4772In a retrospective study of 34 non-small cell lung cancer patients, a lung adenocarcinoma patient with SCN8A deleterious Q427* mutation, treated with pembrolizumab monotherapy, was associated with a d… (full text at CIViC) PMID 25765070 · Rizvi et al., 2015 · Open in CIViC | civic |
| NRG1 Fusion1 | ||||||||
| Afatinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID5859In patient with lung adenocarcinoma an SDC4-NRG1 gene fusion was detected. Integrative genome analysis was used to assess the potential functional significance of the detected gene fusion, prioritizin… (full text at CIViC) PMID 28950338 · Jones et al., 2017 · Open in CIViC | civic |
| ROS1 Fusion1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1690In an evaluation of a patient and never smoker with crizotinib-sensitive lung adenocarcinoma, an SDC4-ROS1 rearrangement was identified using comprehensive genomic profiling. The patient attained a de… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC | civic |
| SDHB Mutation1 | ||||||||
| Metformin + VandetanibCombination | Hereditary Renal Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID7959Vandetanib in Combination With Metformin is tested in Phase II trial in People With HLRCC or SDH-Associated Kidney Cancer or Sporadic Papillary Renal Cell Carcinoma PMID 27325049 · Sidana et al., 2016 · Open in CIViC | civic |
| EGFR Fusion1 | ||||||||
| Cetuximab + GefitinibCombination | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID10899Case report describing a patient with NSCLC and EGFR(ex25)::Intergenic Region of SEC61G(breakpoint 32 aa downstream of SEC61G) fusion and concurrent EGFR amplification with treatment response to a com… (full text at CIViC) PMID 34342091 · Zhang et al., 2021 · Open in CIViC | civic |
| SETD2 Loss2 | ||||||||
| Anti-PD1 Monoclonal Antibody + ATR InhibitorCombination | Clear Cell Renal Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12580In preclinical RCC models (n ≈ 5/group), Setd2 loss enhanced sensitivity to the ATR inhibitor VE822 (60 mg/kg orally, 5 days/week) and anti–PD-1 antibody (100 µg intraperitoneally, every 3 days) reduc… (full text at CIViC) PMID 37527013 · Liu et al., 2023 · Open in CIViC | civic |
| Akt Inhibitor MK2206 + PI3Kbeta Inhibitor AZD8186 + TGX221Substitutes | Clear Cell Renal Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12581In clear cell RCC, SETD2 loss predicts sensitivity to PI3Kβ pathway inhibition: SETD2-deficient 786-0 and SETD2-mutant A498 cells treated with PI3Kβ inhibitors TGX221 or AZD8186 showed reduced viabili… (full text at CIViC) PMID 31695846 · Terzo et al., 2019 · Open in CIViC | civic |
| SLC29A1 Overexpression1 | ||||||||
| Gemcitabine | Pancreatic Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID10145Surgically resected PDACs were used to create tissue microarrays, which were scored for antibody staining of hENT1 (SLC29A1). For patients treated with gemcitabine (n=243), high levels of hENT1 were a… (full text at CIViC) PMID 22705007 · Maréchal et al., 2012 · Open in CIViC | civic |
| NRG1 Fusion3 | ||||||||
| Afatinib | Mucinous Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | rejected | EID7489A 42 year old nonsmoker with metastatic lung adenocarcinoma that was wild-type for EGFR, KRAS, ROS1, and ALK, was found to have re-arranged NRG1. Treatment with afatanib resulted in rapid symptomatic … (full text at CIViC) PMID 28502724 · Gay et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7491A 42 year old nonsmoker with metastatic lung adenocarcinoma that was wild-type for EGFR, KRAS, ROS1, and ALK, was found to have re-arranged NRG1. Treatment with afatanib resulted in rapid symptomatic … (full text at CIViC) PMID 28502724 · Gay et al., 2017 · Open in CIViC | civic |
| Erlotinib + LumretuzumabCombination | Mucinous Adenocarcinoma | Predictive | C | Supports | ||||
| ROS1 Fusion1 | ||||||||
| Crizotinib | Pancreatic Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11651In this case report of a single patient with pancreatic adenocarcinoma was found to harbour a SLC4A4::ROS1 fusion by NGS analysis. Based on the presence of the ROS1 fusion the patient was initiated on… (full text at CIViC) PMID 37079858 · Reutter et al., 2023 · Open in CIViC | civic |
| SLFN11 EXPRESSION1 | ||||||||
| Talazoparib + TemozolomideCombination | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5883SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC as well as combinatorial therapy with TMZ. PMID 27440269 · Lok et al., 2017 · Open in CIViC | civic |
| SMAD4 Expression1 | ||||||||
| (prognostic) | Pancreatic Ductal Adenocarcinoma | Prognostic | B | Supports Better Outcome | 3 | accepted | EID1306In 249 patients that have undergone a pancreaticoduodenectomy (Whipple) for the resection of pancreatic ductal adenocarcinoma, expression of SMAD4 is associated with favorable prognosis. SMAD4 was ass… (full text at CIViC) PMID 11751510 · Tascilar et al., 2001 · Open in CIViC | civic |
| SMAD4 Mutation1 | ||||||||
| (prognostic) | Pancreatic Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID511In a study of 89 patients with adenocarcinoma of the pancreas who underwent a pancreaticoduodenectomy, those with mutations in SMAD4 had shorter overall survival than wild-type patients. PMID 19584151 · Blackford et al., 2009 · Open in CIViC | civic |
| SMAD4 Underexpression1 | ||||||||
| Cetuximab | Head and Neck Squamous Cell Carcinoma | Predictive | D | Supports Resistance | 3 | accepted | EID720In this study, SMAD4 underexpression was associated with an epithelial-to-mesenchymal transition and resistance to EGFR-directed treatment with Cetuximab. PMID 26046389 · Cheng et al., 2015 · Open in CIViC | civic |
| SMARCA4 INACTIVATING MUTATION1 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID513In patients with lung adenocarcinoma, those with loss-of-function mutations in SMARCA4 had worse overall survival than those with only missense or no mutations. PMID 24658004 · Jelinic et al., 2014 · Open in CIViC | civic |
| SMARCB1 Loss2 | ||||||||
| (diagnostic) | Renal Medullary Carcinoma | Diagnostic | B | Supports Positive | 2 | accepted | EID11165In a retrospective analysis of 20 patients with renal medullary carcinoma, all patients had loss of SMARCB1 staining by IHC. FISH revealed 11 (55%) had a SMARCB1 translocation with loss of the second… (full text at CIViC) PMID 30980040 · Jia et al., 2019 · Open in CIViC | civic |
| 〃 | Renal Medullary Carcinoma | Diagnostic | B | Supports Positive | 2 | accepted | EID11167In a comparison of 6 renal medullary carcinomas (RMC) and 22 collecting duct carcinomas (CDC), all 6 RMC were negative for SMARCB1 by IHC whereas only 1 of 22 CDC lost SMARCB1 expressing, supporting S… (full text at CIViC) PMID 22686875 · Calderaro et al., 2012 · Open in CIViC | civic |
| SPRY2 UNDEREXPRESSION1 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID6455The correlation between FGFR2/SPRY2 and clinicopathologic factors was analyzed by Chi-square to screen the FGFR2/SPRY2-relevant factors. SPRY2 low expression was demonstrated to be significantly assoc… (full text at CIViC) PMID 28002800 · Xu et al., 2017 · Open in CIViC | civic |
Data updated 10 hours 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.
| Predictive |
| A |
| Supports Sensitivity Response |
| 5 |
| accepted |
EID12157In this phase III trial, 291 patients (12 years or older) with medullary thyroid cancer harbouring RET mutations were enrolled. Patients were randomized in a 2:1 ratio to receive selpercatinib (n=193)… (full text at CIViC) PMID 37870969 · Hadoux et al., 2023 · Open in CIViC |
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| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID8851In this international phase 1/2 trial (NCT03157128), 55 RET-mutant medullary thyroid cancer patients who had previously received the multi-kinase inhibitors vandetanib and/or cabozantinib received th… (full text at CIViC) PMID 32846061 · Wirth et al., 2020 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID7070In this phase 1 trial, patients with RET-fusion or mutation positive cancers were treated with the selective RET-inhibitor selpercatinib (LOXO-292). Tumor reduction was achieved in 79% of medullary th… (full text at CIViC) | civic |
| 3 |
| submitted |
EID1915Tumor samples from 640 patients with metastatic solid tumors were prospectively analyzed with a next-generation sequencing assay to identify molecular targets. 13 (2%) of 640 patients had a RICTOR-aam… (full text at CIViC) PMID 28028034 · Kim et al., 2017 · Open in CIViC |
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| MTOR Kinase Inhibitor AZD8055 + Sapanisertib + VistusertibSubstitutes | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID1916RICTOR amplification was observed in ca. 14% of 42 SCLC patients with panel sequencing results. 4 cell lines (2 with RICTOR CN gain, 2 without) were tested for the efficacy of mTOR pathway inhibitors.… (full text at CIViC) PMID 27863413 · Sakre et al., 2017 · Open in CIViC | civic |
| 2 |
| submitted |
EID7495Two patients with EGFR/KRAS/ALK wild-type invasive mucinous adenocarcinoma of the lung were found to have SLC3A2-NRG1 fusions. Both patients were treated with combination lumretuzumab, an anti-HER3 mo… (full text at CIViC) PMID 30268483 · Kim et al., 2018 · Open in CIViC |
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