Melanocytic Neoplasm

Dabrafenib with trametinib provides higher response rate and lower toxicity (as compared to chemotherapy) in patients with melanoma.

PMID 24583796 · Menzies et al., 2014 · Open in CIViC

Adjuvant dual treatment with BRAF inhibitor dabrafenib and MEK inhibitor trametinib was administered to patients with stage III resected melenoma with V600E or V600K mutation in this stage III trial (… (full text at CIViC)

PMID 28891408 · Long et al., 2017 · Open in CIViC

In this Phase III trial (NCT01584648 COMBI-d), previously untreated patients with unresectable stage IIIC or IV melanoma with BRAF V600E (359 patients) or V600K (61 patients) received dabrafenib and t… (full text at CIViC)

PMID 25265492 · Long et al., 2014 · Open in CIViC

In 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

In this Phase I and II study (NCT01072175) patients with metastatic melanoma were given dabrafenib and trametinib combination therapy vs. dabrafenib monotherapy. From V600E patients, 45 received monot… (full text at CIViC)

PMID 23020132 · Flaherty et al., 2012 · Open in CIViC

49 BRAF-mutant melanoma cell lines from patients not previously treated with BRAF inhibition were analyzed. 21 exhibited primary resistance to BRAF inhibition using PLX4720. Inhibition of MEK1/2 (AZD6… (full text at CIViC)

PMID 26678033 · Penna et al., 2016 · Open in CIViC

In an in vitro study, a melanoma cell line, A375 (Amelanotic melanoma), expressing the BRAF V600E mutation was associated with resistance to dasatinib treatment, comparable to melanoma MEWO cells expr… (full text at CIViC)

PMID 19671763 · Woodman et al., 2009 · Open in CIViC

This was a phase I expansion and pharmacodynamic study of oral MEK inhibitor RO4987655 on advanced cancer. Of 17 patients with BRAF V600E melanoma, 4 achieved partial response, 5 experienced stable di… (full text at CIViC)

PMID 24947927 · Zimmer et al., 2014 · Open in CIViC

In a mouse in vivo study of MEK protein inhibitor, PD-0325901, was able to suppress growth of SKMEL28 BRAF-V600E xenograft tumors (P<0.01). The reduction of growth was associated with loss of D-cyclin… (full text at CIViC)

PMID 16273091 · Solit et al., 2006 · Open in CIViC

An 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

One patient with BRAF V600E mutated melanoma (with no detected PI3K pathway deregulation) had a partial response on treatment with pictilisib, a PI3K inhibitor, for 9.5 months. Study was a phase-1 wit… (full text at CIViC)

PMID 25370471 · Sarker et al., 2015 · Open in CIViC

Combined nutlin-3 and PLX4720 administration to athymic nude mice subcutanousely injected with the A357 melanoma cell line with a BRAF V600E mutation effectively inhibited tumor growth significantly m… (full text at CIViC)

PMID 23812671 · Ji et al., 2013 · Open in CIViC

In a mouse in vivo study, the MEK protein inhibitor selumetinib suppressed the growth of 1205Lu xenograft tumors, which contains the BRAF-V600Emutation (0.91 +/- 0.10-fold volume increase vs. 9.47 +/-… (full text at CIViC)

PMID 18172275 · Haass et al., 2008 · Open in CIViC

An inducible BRAF-V600E mouse melanoma model has shown a tight correlation between activated BRAF and disease progression.

PMID 16424035 · Hoeflich et al., 2006 · Open in CIViC

In a mouse in vivo study, the dual RAF and VEGF inhibitor sorafenib suppressed the growth of both UACC903 and 1205Lu cell line- generating xenograft tumors harboring the BRAF-V600E mutation, which ha… (full text at CIViC)

PMID 15781657 · Sharma et al., 2005 · Open in CIViC

An inducible BRAF-V600E mouse melanoma model has shown a tight correlation between activated BRAF and disease progression.

PMID 16424035 · Hoeflich et al., 2006 · Open in CIViC

In a study of 322 advanced melanoma patients with BRAF-V600E (N=281), BRAF-V600K (N=40), or both mutations (N=1), treatment with trametinib was associated with improved progression-free survival (4.8m… (full text at CIViC)

PMID 22663011 · Flaherty et al., 2012 · Open in CIViC

An 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

An 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

In the setting of BRAF(V600E), NF1 loss resulted in elevated activation of RAS-GTP but does not show resistance to MEK inhibitors.

PMID 24576830 · Nissan et al., 2014 · Open in CIViC

Phase 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

The BRIM-3 Phase III trial NCT01006980 assessed BRAF inhibitor vemurafenib versus dacarbazine in 598 patients with treatment naive metastatic melanoma and confirmed V600E mutation. Significant differe… (full text at CIViC)

PMID 24508103 · McArthur et al., 2014 · Open in CIViC

Multicenter, phase 1, dose-escalation trial of PLX4032 (Vemurafenib). Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or p… (full text at CIViC)

PMID 20818844 · Flaherty et al., 2010 · Open in CIViC

In a phase 2 clinical trial (NCT00949702) of 132 BRAF mutation positive metastatic melanoma patients treated with vemurafenib monotherapy, patients harboring BRAF V600E (n=123) or V600K (n=9) mutation… (full text at CIViC)

PMID 23569304 · Trunzer et al., 2013 · Open in CIViC

In a clinical study (NCT01307397) of Polish, stage IIIC/IV, melanoma patients with metastases (n=75) harboring BRAF V600 mutation (as detected by cobas 4800 BRAF V600 Mutation Test), median overall su… (full text at CIViC)

PMID 26557775 · Rutkowski et al., 2015 · Open in CIViC

In a retrospective study of 300 stage IV melanoma patients, patients with BRAF V600E mutation (n=175) were associated with a 4.8% (8/167) complete response, a 58.1% (97/167) partial response and stabl… (full text at CIViC)

PMID 25524477 · Ugurel et al., 2015 · Open in CIViC

In a retrospective study of 30 metastatic melanoma patients with progressing metastases, patients with BRAF V600E mutation (n=8) treated with vemurafenib monotherapy achieved a partial response (n=5) … (full text at CIViC)

PMID 24463458 · Rizos et al., 2014 · Open in CIViC

In a stage I melanoma patient harboring a BRAF V600E mutation, response to vemurafenib monotherapy was reported. Upon identification of the BRAF V600E mutation, the patient enrolled in a clinical tria… (full text at CIViC)

PMID 24616537 · Ashworth et al., 2014 · Open in CIViC

In a conjunctival malignant melanoma patient harboring a BRAF V600E mutation, BRAF V600E was associated with response to vemurafenib treatment. Prior to identification of the BRAF V600E mutation, the … (full text at CIViC)

PMID 27520988 · Maleka et al., 2016 · Open in CIViC

In an in vitro study, several cell lines (including MALME-3M, Colo829, Colo38, A375 and SK-MEK28) expressing BRAF V600E were associated with increased sensitivity to vemurafenib (RG7204) treatment, as… (full text at CIViC)

PMID 20551065 · Yang et al., 2010 · Open in CIViC

In an in vitro study of 27 melanoma cell lines, 18 out of 20 cell lines expressing BRAF V600E mutation were associated with sensitivity to vemurafenib treatment (IC50: 0.01-1�M). Sensitivity was deter… (full text at CIViC)

PMID 22241959 · Vergani et al., 2011 · Open in CIViC

Acquired resistance to vemurafenib in BRAF V600E-positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRB upregulation or NRAS mutations resulting in M… (full text at CIViC)

PMID 21107320 · Johannessen et al., 2010 · Open in CIViC

Acquired resistance to vemurafenib in BRAF V600E-positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRB upregulation or NRAS mutations resulting in M… (full text at CIViC)

PMID 21107323 · Nazarian et al., 2010 · Open in CIViC

In an in vitro study, cell lines (including YUHUY and YUSAC2) expressing BRAF V600E were associated with increased sensitivity to vemurafenib (PLX4032) treatment, as compared to cell lines expressing … (full text at CIViC)

PMID 20149136 · Halaban et al., 2010 · Open in CIViC

In an in vitro study, BRAF V600E expressing cell lines (COLO205, A375 and COLO829) demonstrated improved sensitivity to vemurafenib treatment, compared to BRAF wild-type expressing cells. Sensitivity … (full text at CIViC)

PMID 18287029 · Tsai et al., 2008 · Open in CIViC

In an in vitro study, a MBA72 cell line expressing BRAF V600E demonstrated improved sensitivity to vemurafenib treatment, compared to LND-1 cells expression BRAF wild-type. Sensitivity was determined … (full text at CIViC)

PMID 26070258 · Porcelli et al., 2015 · Open in CIViC

An 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

In this Phase III trial (coBRIM, NCT01689519) of 495 V600 mutant melanoma patients, 344 had V600E mutation. 174 patients were treated with vemurafenib and placebo, and 170 were treated with vemurafeni… (full text at CIViC)

PMID 25265494 · Larkin et al., 2014 · Open in CIViC

A single 66-year old male patient with advanced melanoma thought to have concomitant BRAF V600E and V600M mutations responded rapidly to dabrafenib. His shoulder lesion reduced by 60% after 1 week of … (full text at CIViC)

PMID 23031422 · Ponti et al., 2012 · Open in CIViC

Experiment with immunodeficient mice transplanted with melanoma cell lines indicates EZH2 inhibitor JQEZ5 might be effective in combination with a B-RAF inhibitor in RAF-mutant melanoma.

PMID 27135738 · Souroullas et al., 2016 · Open in CIViC

In vitro studies of M229 (a human melanoma cell line) endogenously expressing wildtype KRAS and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that cells virally induced to stably over… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E or V600K (known BRAF inhibitor sensitizing mutations), MAPK pathway reactivation mechanisms were implicated in acquired r… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

In the setting of BRAF(V600E), NF1 loss resulted in elevated activation of RAS-GTP and resistance to RAF inhibitors.

PMID 24576830 · Nissan et al., 2014 · Open in CIViC

In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E or V600K (known BRAF inhibitor sensitizing mutations), MAPK pathway reactivation mechanisms were implicated in acquired r… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

An in vitro study of M229 (a human melanoma cell line) endogenously expressing wildtype PIK3CA and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that cells induced to stably over-expr… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

An in vitro study of WM2664 (a human melanoma cell line) endogenously expressing wildtype PIK3R2 and BRAF V600D (a known BRAF inhibitor sensitizing mutation) found that cells virally induced to stably… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

Most BRAF mutant cell lines (mostly V600E) with PTEN mutation or loss of expression were among those sensitive to inhibition with AKT inhibitor GSK2141795B.

PMID 24735930 · Lassen et al., 2014 · Open in CIViC

Several BRAF V600E mutant melanoma cell lines (M249, M399, M397AR)) with PTEN mutation or loss of expression were among those sensitive to combination dabrafenib plus AKT inhibitor GSK2141795B, as mea… (full text at CIViC)

PMID 24735930 · Lassen et al., 2014 · Open in CIViC

This was a Phase I and II study (NCT01072175) of dabrafenib and trametinib combination therapy vs. dabrafenib monotherapy in patients with metastatic melanoma. Cutaneous squamous-cell carcinoma was… (full text at CIViC)

PMID 23020132 · Flaherty et al., 2012 · Open in CIViC

Phase 2 trial in 132 patients with previously treated metastatic melanoma with BRAF V600E (n=122) or V600K (n=10) mutation. Confirmed overall response rate was 53% (95% confidence interval [CI], 44 t… (full text at CIViC)

PMID 22356324 · Sosman et al., 2012 · Open in CIViC