Cancer Family
Skin Neoplasm
CI-CAN-00000051Explore in graph →
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Cancer Family
CI-CAN-00000051Explore in graph →
Variants & evidence
112 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 |
|---|---|---|---|---|---|---|---|---|
| AEBP1 Overexpression1 | ||||||||
| Vemurafenib | Cutaneous MelanomaALIAS | Predictive | D | Supports Resistance | 2 | submitted | EID2911To identify novel molecular mechanism(s) of resistance, we generated PLX4032-resistant cell lines by chronic exposure of the BRAF (V600E)-positive parental melanoma cell line Mel-CV to PLX4032. After … (full text at CIViC) PMID 24201813 · Hu et al., 2013 · Open in CIViC | civic |
| BRAF Fusion1 | ||||||||
| Trametinib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID13150A 42 year old male patient with stage III cutaneous melanoma harboring an AGAP3::BRAF fusion was treated with the MEK inhibitor trametinib after prior pembrolizumab and experienced a response lasting … (full text at CIViC) PMID 35871080 · Moran et al., 2022 · Open in CIViC | civic |
| ALK Alternative Transcript (ATI)1 | ||||||||
| Crizotinib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID1936Expression of an alternative ALK transcript (ATI), encompassing exons 20–29 preceded by ~400 base pairs (bp) of intron 19, but not exons 1–19 was identified in three samples of thyroid cancer and mela… (full text at CIViC) PMID 26444240 · Wiesner et al., 2015 · Open in CIViC | civic |
| B2M S14FS1 | ||||||||
| Pembrolizumab | Cutaneous MelanomaALIAS | Predictive | C | Supports Resistance | 3 | accepted | EID1569Paired tumor samples were analyzed from four patients with metastatic melanoma and initial response with a subsequent relapse under pembrolizumab (PD-1 checkpoint inhibitor) therapy. Baseline biopsies… (full text at CIViC) PMID 27433843 · Zaretsky et al., 2016 · Open in CIViC | civic |
| BRAF D594A1 | ||||||||
| Mitogen-Activated Protein Kinase Kinase Inhibitor + SorafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | E | Supports Sensitivity Response | 3 | accepted | EID1454Preclinical study in melanoma cell lines. Inactivity of BRAF as mediated by specific mutation (D594A, D594V or K483M) or selective pharmacological inhibition leads to MEK hyperactivation through CRAF … (full text at CIViC) PMID 20141835 · Heidorn et al., 2010 · Open in CIViC | civic |
| BRAF D594G2 | ||||||||
| Sorafenib | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID6001In this preclinical study, melanoma cell lines harboring the kinase-dead G469E- and D594G mutations were identified. These cell lines were resitant to MEK-Inhibition but underwent apoptosis after shRN… (full text at CIViC) PMID 18794803 · Smalley et al., 2009 · Open in CIViC | civic |
| U0126 | Cutaneous MelanomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6002In this preclinical study, melanoma cell lines harboring the kinase-dead G469E- and D594G mutations were identified. These cell lines were resitant to MEK-Inhibition but underwent apoptosis after shRN… (full text at CIViC) PMID 18794803 · Smalley et al., 2009 · Open in CIViC | civic |
| BRAF D594N5 | ||||||||
| Dabrafenib | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | — | rejected | EID2813Patients were treated with a specific RAF inhibitor (dabrafenib), which improved overall survival of patients with BRAF mutations (P<0.003), compared to non-treated patients with BRAF mutations. Patie… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC | civic |
| 〃 | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | — | rejected | EID2814An inducible BRAF-V600E mouse melanoma model shows a tight correlation between activated BRAF and disease progression. PMID 16424035 · Hoeflich et al., 2006 · Open in CIViC | civic |
| 〃 | Cutaneous MelanomaALIAS | Predictive | ||||||
| BRAF D594V1 | ||||||||
| Sorafenib + TrametinibSubstitutes | Cutaneous MelanomaALIAS | Predictive | E | Supports Sensitivity Response | 3 | accepted | EID1456Preclinical study in melanoma cell lines. Inactivity of BRAF as mediated by specific mutation (D594A, D594V or K483M) or selective pharmacological inhibition leads to MEK hyperactivation through CRAF … (full text at CIViC) PMID 20141835 · Heidorn et al., 2010 · Open in CIViC | civic |
| BRAF G469E2 | ||||||||
| Sorafenib | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID6003In this preclinical study, melanoma cell lines harboring the kinase-dead G469E- and D594G mutations were identified. These cell lines were resitant to MEK-Inhibition but underwent apoptosis after shRN… (full text at CIViC) PMID 18794803 · Smalley et al., 2009 · Open in CIViC | civic |
| U0126 | Cutaneous MelanomaALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID6004In this preclinical study, melanoma cell lines harboring the kinase-dead G469E- and D594G mutations were identified. These cell lines were resitant to MEK-Inhibition (U0126) but underwent apoptosis af… (full text at CIViC) PMID 18794803 · Smalley et al., 2009 · Open in CIViC | civic |
| BRAF K483M1 | ||||||||
| Mitogen-Activated Protein Kinase Kinase Inhibitor + SorafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | E | Supports Sensitivity Response | 3 | accepted | EID1457Preclinical study in melanoma cell lines. Inactivity of BRAF as mediated by specific mutation (D594A, D594V or K483M) or selective pharmacological inhibition leads to MEK hyperactivation through CRAF … (full text at CIViC) PMID 20141835 · Heidorn et al., 2010 · Open in CIViC | civic |
| BRAF K601E2 | ||||||||
| Dabrafenib | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | — | submitted | EID2812In a study of 197 metastatic melanoma patients, BRAF mutations were identified in 95 patients including V600E (n=70), V600K (n=19), K601E (n=1) and D594N (n=1). Patients were treated with a specific R… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC | civic |
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1462Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597Q2 | ||||||||
| Trametinib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4905Case study report including one patient with L597Q mutation-positive metastatic melanoma (M1b disease) treated with the MEK inhibitor trametinib. The L597Q patient achieved a RECIST partial response a… (full text at CIViC) PMID 24933606 · Bowyer et al., 2014 · Open in CIViC | civic |
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1461Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597R1 | ||||||||
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1458Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597S2 | ||||||||
| MEK Inhibitor REC-4881 | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1460Case report of a 69 year old patient with metastatic melanoma treated with MEK inhibitor TAK-733 in a clinical trial. A partial radiographic response with a decrease of 31% in the sum of maximum diame… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1459Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597V1 | ||||||||
| Trametinib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1463Case report of a phase 1 study in advanced melanoma patients. 97 patients with melanoma were enrolled and treated with trametinib. One patient with a BRAF Leu597Val had a confirmed partial response wi… (full text at CIViC) PMID 22805292 · Falchook et al., 2012 · Open in CIViC | civic |
| BRAF V6001 | ||||||||
| Dabrafenib + TrametinibCombination | Cutaneous MelanomaALIAS | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1411The Combi-v (NCT01597908) open-label, randomized phase 3 trial had 704 patients with metastatic melanoma with a BRAF V600 mutation. Patients were randomized to receive either a combination of dabrafen… (full text at CIViC) PMID 25399551 · Robert et al., 2015 · Open in CIViC | civic |
| BRAF V600E3 | ||||||||
| Dabrafenib | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | — | submitted | EID2146In a phase 2 clinical trial with 250 metastatic melanoma BRAF-V600E patients, treatment groups were randomly assigned to either dabrafenib, BRAF specific inhibitor, (n=187) or dacarbazine, a standard… (full text at CIViC) PMID 22735384 · Hauschild et al., 2012 · Open in CIViC | civic |
| Dabrafenib + TrametinibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID3758In a clinical trial (NCT01597908) of 704 metastatic melanoma patients, patients harboring a BRAF V600E mutation and treated with vemurafenib (n=317) were associated with a 51% response rate, as compar… (full text at CIViC) PMID 25399551 · Robert et al., 2015 · Open in CIViC | civic |
| Vemurafenib | Cutaneous Melanoma | |||||||
| BRAF V600K2 | ||||||||
| Binimetinib + EncorafenibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID13183In the randomized phase III COLUMBUS trial of patients with locally advanced unresectable or metastatic BRAF V600-mutant melanoma, 22 patients with BRAF V600K received encorafenib plus binimetinib and… (full text at CIViC) PMID 29573941 · Dummer et al., 2018 · Open in CIViC | civic |
| Dabrafenib + TrametinibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4181In a phase 3 clinical trial (NCT01597908) involving 704 patients with metastatic melanoma harboring BRAF V600 mutations, a subgroup analysis of patients with V600K mutations showed an objective respon… (full text at CIViC) PMID 25399551 · Robert et al., 2015 · Open in CIViC | civic |
| BRAF V600_K601DELINSD1 | ||||||||
| Vemurafenib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | — | submitted | EID4789In a stage IV cutaneous nodular thoracic melanoma patient with pulmonary, liver and brain metastases, harboring a BRAF V600_K601delinsD mutation, stable disease to vemurafenib monotherapy was reported… (full text at CIViC) PMID 25265970 · Trudel et al., 2014 · Open in CIViC | civic |
| BRAF V600R2 | ||||||||
| Vemurafenib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID4172An 81 year old male was diagnosed with ulcerated cutaneous melanoma of the occiput (M1c), and had undergone several local resections and radiotherapy. A metastasis was found to harbor BRAF V600R mutat… (full text at CIViC) PMID 23237741 · Klein et al., 2013 · Open in CIViC | civic |
| Dabrafenib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | B | Does Not Support Resistance | 2 | submitted | EID8948Nine patients with BRAF V600R mutated metastatic melanoma were given dabrafenib (n=7) or vemurafenib (n=2) monotherapy as part of a compassionate access program. Five out of six radiographically asses… (full text at CIViC) PMID 23237741 · Klein et al., 2013 · Open in CIViC | civic |
| CCND1 Amplification1 | ||||||||
| Carboplatin + Paclitaxel + SorafenibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID1495Retrospective analysis of somatic mutations and copy number changes in 119 patient treated with carboplatin, paclitaxel, ± sorafenib (CPS) in the E2603 trial. CPS therapy was associated with improved … (full text at CIViC) PMID 26307133 · Wilson et al., 2016 · Open in CIViC | civic |
| CDK4 R24C1 | ||||||||
| Palbociclib | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID1376In a cohort of 143 patients with primary invasive melanoma, copy-number gain of CDK4 was observed (FISH) in 37% of cases. PD0332991 efficacy (proliferation assay) was assessed in a panel of 47 melanom… (full text at CIViC) PMID 24495407 · Young et al., 2014 · Open in CIViC | civic |
| CDKN2A Loss3 | ||||||||
| Alvocidib | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1372Preclinical study in 9 melanoma cell lines. Three cell lines did not have CDKN2A (p16) mutations and showed expression of the protein on western blot analysis. Two of the other six cell lines had stop… (full text at CIViC) PMID 12777976 · Robinson et al., 2003 · Open in CIViC | civic |
| Palbociclib | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1375In a cohort of 143 patients with primary invasive melanoma hemizygous or homozygous loss of CDKN2A was observed (FISH) in 56% of cases. PD0332991 efficacy (proliferation assay) was assessed in a panel… (full text at CIViC) PMID 24495407 · Young et al., 2014 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Predictive | ||||||
| PDGFB Fusion12 | ||||||||
| (diagnostic) | Dermatofibrosarcoma Protuberans | Diagnostic | B | Supports Positive | 4 | accepted | EID9787This study analyzed 27 formalin-fixed-paraffin-embedded samples of patients with known dermatofibrosarcoma protuberans (DFSP) using a newly designed multiplex RT-PCR assay. The assay identified COL1A1… (full text at CIViC) PMID 17950782 · Patel et al., 2008 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Diagnostic | B | Supports Positive | 4 | accepted | EID12417The authors studied 27 archival formalin-fixed, paraffin-embedded (FFPE) samples of dermatofibrosarcoma protuberans (DFSP) cases obtained from Texas Children's Hospital and University of Texas MD Ande… (full text at CIViC) PMID 17950782 · Patel et al., 2008 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Diagnostic | B | Supports Positive | ||||
Data updated 15 minutes 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.
| D |
| Supports Sensitivity Response |
| — |
| rejected |
EID2815Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRbeta upregulation or NRAS mutations resulting i… (full text at CIViC) PMID 20818844 · Flaherty et al., 2010 · Open in CIViC |
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| 〃 | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | — | rejected | EID2816Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRbeta upregulation or NRAS mutations resulting i… (full text at CIViC) PMID 21107320 · Johannessen et al., 2010 · Open in CIViC | civic |
| 〃 | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | — | rejected | EID2817Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRbeta upregulation or NRAS mutations resulting i… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC | civic |
| Predictive |
| A |
| Supports Sensitivity Response |
| 5 |
| accepted |
EID1409Phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. At 6 months, overall survival was … (full text at CIViC) PMID 21639808 · Chapman et al., 2011 · Open in CIViC |
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| D |
| Supports Sensitivity Response |
| 2 |
| accepted |
EID1881An imatinib-resistant cell line, DFSP105, was established from a dermatofibrosarcoma protuberans which had progressed to a high-grade fibrosarcomatous DFSP. The disease-associated COL1A1-PDGFB fusion … (full text at CIViC) PMID 25852058 · Eilers et al., 2015 · Open in CIViC |
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| 4 |
| accepted |
EID12418In this study, paraffin-embedded tissue microarray (TMA) evaluation of translocation t(17;22)(q22;q13) was performed on 40 tissue samples from 24 female and 16 male DFSP patients (37 primary tumors, 3… (full text at CIViC) PMID 21111450 · Segura et al., 2011 · Open in CIViC |
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| (oncogenic) | Dermatofibrosarcoma Protuberans | Oncogenic | B | Supports Oncogenicity | 3 | accepted | EID10314In this study, 57 cases of dermatofibrosarcoma protuberans (DFSP) were evaluated. The COL1A1-PDGFB fusion was detected in 42 (74%) out of the 57 sample after performing targeted PCR amplification and … (full text at CIViC) PMID 17431412 · Takahira et al., 2007 · Open in CIViC | civic |
| (diagnostic) | Dermatofibrosarcoma Protuberans | Diagnostic | B | Supports Positive | 3 | accepted | EID11729In this 2022 study by Peng et al., the authors performed whole-genome sequencing on 53 tumor-normal pairs from patients with Dermatofibrosarcoma Protuberans (DFSP) to define its comprehensive genomic … (full text at CIViC) PMID 35441365 · Peng et al., 2022 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Diagnostic | C | Supports Positive | 3 | accepted | EID12416The is a cytogenetic case study of a 10-year-old female with pure pigmented dermatofibrosarcoma protuberans (DFSP), also called Bednar tumor, on her right shoulder. Karyotype of tumor cells was 47,XX … (full text at CIViC) PMID 16843106 · Craver et al., 2006 · Open in CIViC | civic |
| Imatinib | Dermatofibrosarcoma Protuberans | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11271In this phase II, open-label, single-arm trial, 106 patients with 40 different malignancies were enrolled (78.5% solid tumors, 21.5% hematologic malignancies), including 12 with COL1A1-PDGFB fusion-po… (full text at CIViC) PMID 18451237 · Heinrich et al., 2008 · Open in CIViC | civic |
| Imatinib Mesylate | Dermatofibrosarcoma Protuberans | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID10336In this non-controlled phase 2 clinical trial, 25 patients with primary or recurrent Dermatofibrosarcoma Protuberans (DFSP) were recruited. Only 21 had the t(17;22) COL1A-PDGFB fusion as detected thro… (full text at CIViC) PMID 20439456 · Kérob et al., 2010 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID10332Ten patients with Dermatofibrosarcoma Protuberans (DFSP) were enrolled in phase II study to investigate the response to imatinib in locally advanced or metastatic DFSP. Eight of the ten patients had l… (full text at CIViC) PMID 15681532 · McArthur et al., 2005 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID10334In this study, DFSP-transformed cell lines (4A and 5A) were used in-vitro and in-vivo to investigate the possibility of blocking the autocrine loop that forms as a result of the t(17;22) COL1A1-PDGFB … (full text at CIViC) PMID 11291071 · Greco et al., 2001 · Open in CIViC | civic |
| 〃 | Dermatofibrosarcoma Protuberans | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID10335In this study, NIH3T3 cell lines were used to characterize the COLIA1/PDGFB fusion protein functionally and structurally in Dermatofibrosarcoma Protuberans (DFSP). The cell lines B5/5 (COLIA1/PDGFB tr… (full text at CIViC) PMID 10446987 · Shimizu et al., 1999 · Open in CIViC | civic |
| Sunitinib | Dermatofibrosarcoma Protuberans | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7991A 37-year-old man presented with dermatofibrosarcoma protuberans (DFSP). Post resection, multiple nodular metastases were found in both lungs and the disease progressed following treatments with cytot… (full text at CIViC) PMID 29760553 · Xiao et al., 2018 · Open in CIViC | civic |