Subtype
Neuroendocrine Carcinoma
CI-CAN-00001275NECExplore in graph →
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Subtype
CI-CAN-00001275NECExplore in graph →
Variants & evidence
50 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 |
|---|---|---|---|---|---|---|---|---|
| CD274 Expression1 | ||||||||
| Pembrolizumab | Merkel Cell Carcinoma | Predictive | B | Does Not Support Sensitivity Response | 2 | accepted | EID1578Patients with Merkel Cell Carcinoma (n=26) were enrolled to receive pembrolizumab. Of these patients, 25 were evaluated for response rate to pembrolizumab and PD-L1 (CD274) expression. The response ra… (full text at CIViC) PMID 27093365 · Nghiem et al., 2016 · Open in CIViC | civic |
| BEND2 Fusion1 | ||||||||
| (oncogenic) | Pancreatic Neuroendocrine CarcinomaALIAS | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID9219A 35 year-old patient presented with a grade 3 pancreatic neuroendocrine tumor and liver metastasis. Whole genome sequencing and RNAseq revealed a previously undescribed somatic translocation between … (full text at CIViC) PMID 31160355 · Williamson et al., 2019 · Open in CIViC | civic |
| CHEK1 Overexpression1 | ||||||||
| Cisplatin + Olaparib + PrexasertibCombination | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID4874A preclinical study to evaluate the efficacy of targeting the overexpressed CHEK1 cell cycle chekpoint kinase, including both miRNA and Prexasertib-induced inhibition. Both in vitro and in vivo, Prexa… (full text at CIViC) PMID 28490518 · Sen et al., 2017 · Open in CIViC | civic |
| DLL3 Expression2 | ||||||||
| Rovalpituzumab Tesirine | Lung Small Cell Carcinoma | Predictive | B | Does Not Support Sensitivity Response | 4 | submitted | EID7764In a phase II trial, patients with DLL3-expressing small cell lung carcinoma were treated with rovalpituzumab tesirine. Only patients with 1% or more tumor cells expressing DLL3 were enrolled. In this… (full text at CIViC) PMID 31506387 · Morgensztern et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Small Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID591974 patients with small-cell lung cancer and eight with large-cell neuroendocrine carcinoma received at least one dose of rovalpituzumab tesirine in a phase 1 trial. 11 (18%) of 60 assessable patients … (full text at CIViC) PMID 27932068 · Rudin et al., 2017 · Open in CIViC | civic |
| EGFR L858R1 | ||||||||
| Erlotinib | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID4293In an in vitro study using NCI-H3255 cells (EGFR L858R mutation), inhibition of EGFR phosphorylation was used as an assay to determine sensitivity to EGFR tyrosine kinase inhibitors. NCI-H3255 cells d… (full text at CIViC) PMID 24893891 · Cross et al., 2014 · Open in CIViC | civic |
| ERBB2 Amplification1 | ||||||||
| Irinotecan + TrastuzumabCombination | Lung Small Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID1044This report details 2 case studies in relapsed HER2 positive SCLC. In the first case, a 50 pack-year patient showed intense non-mutant HER2 expression by IHC without DNA amplification, and had underg… (full text at CIViC) PMID 25601188 · Kinehara et al., 2015 · Open in CIViC | civic |
| KIT M541L1 | ||||||||
| (diagnostic) | Merkel Cell Carcinoma | Diagnostic | B | Does Not Support Positive | 3 | submitted | EID9698Study evaluated 42 cases with aggressive fibromatosis were genotyped for the M541L (c.1621 A>C; rs3822214) was evaluated and compared to gender- and age-matched 126 healthy controls. In 4/7 cases with… (full text at CIViC) PMID 21757432 · Grabellus et al., 2011 · Open in CIViC | civic |
| MET R988C + MET T1010I1 | ||||||||
| (oncogenic) | Lung Small Cell Carcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11370Patient small-cell lung cancer cells with c-MET juxtamembrane mutations (R988C or T1010I) were shown to have increased tyrosine phosphorylated cellular proteins such as paxillin, a focal adhesion cyto… (full text at CIViC) PMID 14559814 · Ma et al., 2003 · Open in CIViC | civic |
| MYC Overexpression1 | ||||||||
| Cisplatin + Olaparib + PrexasertibCombination | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID3003A preclinical study to evaluate the efficacy of targeting the overexpressed CHEK1 cell cycle chekpoint kinase, including both miRNA and Prexasertib-induced inhibition. Both in vitro and in vivo, Prexa… (full text at CIViC) PMID 28490518 · Sen et al., 2017 · Open in CIViC | civic |
| PIK3CA P471L1 | ||||||||
| Idelalisib | Merkel Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID739A case report of an 86-year old patient with metastasized Merkel cell carcinoma who achieved a complete clinical response under therapy with the PI3K-inhibitor Idelalisib. PMID 26466009 · Shiver et al., 2015 · Open in CIViC | civic |
| RAD50 L1237F1 | ||||||||
| Checkpoint Kinase Inhibitor AZD7762 + IrinotecanCombination | Ureter Small Cell Neuroendocrine CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID5829A 51-year-old woman with an invasive small-cell cancer of the ureter showed a durable complete response at 3-years when treated with AZD7762 (an ATP-competitive checkpoint kinase inhibitor) and irinot… (full text at CIViC) PMID 24934408 · Al-Ahmadie et al., 2014 · Open in CIViC | civic |
| RB1 Mutation1 | ||||||||
| Chemotherapy | Lung Small Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID1866Study evaluated a total of 50 small cell lung cancer patients with extensive stage disease. Multivariate analysis identified RB1 as a factor in predicting response to first-line chemotherapy (odds rat… (full text at CIViC) PMID 26802149 · Dowlati et al., 2016 · Open in CIViC | civic |
| RET C609Y2 | ||||||||
| (predisposing) | Thyroid Gland Medullary CarcinomaALIAS | Predisposing | B | Supports Predisposition | 4 | accepted | EID2913Study of a family with three generations of history indicating co-segregation of RET C609Y and multiple endocrine neoplasia type 2A, many of whom exhibited medullary thyroid cancers specifically. 22 … (full text at CIViC) PMID 19472011 · Calva et al., 2009 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predisposing | E | Supports Uncertain Significance | 3 | submitted | EID2914This study performed various functional characterizations of several RET mutations known to occur as pathogenic germline variants in multiple endocrine neoplasia type 2 and medullary thyroid cancer. S… (full text at CIViC) PMID 16715139 · Mise et al., 2006 · Open in CIViC | civic |
| RET C634R1 | ||||||||
| (diagnostic) | Thyroid Gland Medullary CarcinomaALIAS | Diagnostic | B | Supports Positive | 3 | submitted | EID4894Sixty-nine individuals from 12 different families presented a codon 634 mutation, the most prevailing missense mutation in our series. The specific mutations identified were C634Y (n = 49), C634R (n =… (full text at CIViC) PMID 12788868 · Puñales et al., 2003 · Open in CIViC | civic |
| RET C634W2 | ||||||||
| Axitinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | D | Supports Resistance | — | submitted | EID3694In an in vitro study, a MTC-TT cell line expressing RET C634W mutation (endogenous) demonstrated resistance to axitinib treatment (IC50: 1.56uM). Resistance was determined by assessing cell viability… (full text at CIViC) PMID 21470995 · Verbeek et al., 2011 · Open in CIViC | civic |
| Motesanib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID75Medullary thyroid cancer cells with RET C634W mutation are insensitive to motesanib, compared to wild-type RET. PMID 21422803 · Coxon et al., 2012 · Open in CIViC | civic |
| RET D378_G685>E1 | ||||||||
| Selpercatinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID11658A 15-year-old boy with metastatic medullary thyroid carcinoma harboring an RET exon 6 deletion (D378_G685>E), previously treated sequentially with four multitargeted kinase inhibitors (vandetanib, sun… (full text at CIViC) PMID 32923911 · Ortiz et al., 2020 · Open in CIViC | civic |
| RET D898_E901del + RET E632_L633del1 | ||||||||
| (oncogenic) | Thyroid Gland Medullary CarcinomaALIAS | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12710In a study of 56 Medullary Thyroid Cancer patients (50 somatic and 6 hereditary) two patients had somatic p.E632_L633del. One of them had p.E632_L633del and p.D898_E901del found in lymph node metasta… (full text at CIViC) PMID 29515777 · Romei et al., 2018 · Open in CIViC | civic |
| RET E632_L633del3 | ||||||||
| Selpercatinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID11875Among 319 medullary thyroid cancer patients enrolled in the LIBRETTO-001 trial, 9 patients harbored the RET p.E632_L633del mutation (c.1894_1899delGAGCTG) in their tumor. After treatment with the sel… (full text at CIViC) PMID 37376747 · Szymczak et al., 2023 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12716A patient with advanced progressive medullary thyroid cancer and distant metastatic disease harbored the somatic RET E632_L633del indel and was treated under the LIBRETTO-201 (NCT03906331) trial. Selp… (full text at CIViC) PMID 35616103 · Elisei et al., 2022 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary Carcinoma | |||||||
| RET G810S1 | ||||||||
| Pralsetinib + SelpercatinibSubstitutes | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Resistance | 4 | submitted | EID8919Cell-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 M918T10 | ||||||||
| (oncogenic) | Thyroid Gland Medullary CarcinomaALIAS | Oncogenic | B | Supports Oncogenicity | 3 | accepted | EID12800In 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 |
| (prognostic) | Thyroid Gland Medullary CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 2 | accepted | EID78In a study of 64 patients (48 kindreds), 62 had germline mutations at known hotspots in RET. Patients with RET M918T mutation were associated with MEN 2B subtype and developed larger and more aggressi… (full text at CIViC) PMID 9839497 · Egawa et al., 1998 · Open in CIViC | civic |
| (predisposing) | Thyroid Gland Medullary CarcinomaALIAS | |||||||
| RET G810S + RET M918T1 | ||||||||
| Selpercatinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Resistance | 3 | accepted | EID8196In two out of three patients with MTC treated in a phase1/2 trial, the RET G810 mutation emerged in ctDNA together with an acquired resistance after initial response to selpercatinib. PMID 31988000 · Solomon et al., 2020 · Open in CIViC | civic |
| 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 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 Amplification2 | ||||||||
| 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 |
| 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 |
| 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 |
| YES1 Amplification + YES1 Overexpression1 | ||||||||
| CH6953755 + DasatinibSubstitutes | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12556In preclinical small cell lung carcinoma (SCLC) models with YES1 amplification or high expression, treatment with the YES1 inhibitor CH6953755 (30 mg/kg, q2d) or dasatinib (45 mg/kg daily) produced ma… (full text at CIViC) PMID 35988891 · Redin et al., 2022 · Open in CIViC | civic |
Data updated 15 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 |
| C |
| Does Not Support Sensitivity Response |
| 2 |
| submitted |
EID12714A 35 yr old man presented with a 9 month history of worsening right side flank pain and no significant family history. Calcitonin was elevated. After imaging, total thyroidectomy with modified radica… (full text at CIViC) PMID 36416226 · Wijewardene et al., 2023 · Open in CIViC |
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| Predisposing |
| C |
| Supports Predisposition |
| 2 |
| accepted |
EID12711A total of 56 metastatic medullary thyroid cancer cases (50 sporadic, 6 familial) were analyzed for RET mutations. A total of 7 cases were found to have a RET germline mutations however one case had a… (full text at CIViC) PMID 29515777 · Romei et al., 2018 · Open in CIViC |
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| Axitinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | D | Supports Resistance | — | submitted | EID3696In an in vitro study, a MZ-CRC-1 cell line expressing RET M918T mutation (endogenous) demonstrated resistance to axitinib treatment (IC50> 5uM). Resistance was determined by assessing cell viability. PMID 21470995 · Verbeek et al., 2011 · Open in CIViC | civic |
| Cabozantinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7710In 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 |
| JAK2 Inhibitor AZD1480 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID77The use of AZD1480 on RET-mutated/rearranged cell lines in vitro led to strong repression of tyroid cancer cell growth. PMID 23056499 · Couto et al., 2012 · Open in CIViC | civic |
| Motesanib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID76Medullary thyroid cancer cells with RET M918T mutation are insensitive to motesanib, compared to wild-type RET. PMID 21422803 · Coxon et al., 2012 · Open in CIViC | civic |
| Selpercatinib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID12598The Phase 3 trial for the selective and brain-penetrant RET kinase inhibitor selpercatinib in Medullary Thyroid Cancer (MTC) LIBRETTO-531 (NCT04211337) consisted of 291 total patients. The patients … (full text at CIViC) PMID 37870969 · Hadoux et al., 2023 · Open in CIViC | civic |
| 〃 | Thyroid Gland Medullary CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | rejected | EID11306After 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 |
| Sorafenib | Thyroid Gland Medullary CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1365In a phase 2 clinical trial of sorafenib in patients with hereditary or sporadic advanced medullary thyroid cancer, 10 out of 12 patients genotyped in arm B (sporadic MTC) tested positive for RET muta… (full text at CIViC) PMID 20368568 · Lam et al., 2010 · Open in CIViC | civic |
| 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 |