Melanoma BRAF Inhibitors Review
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Melanoma BRAF Inhibitors Review
Zelboraf (vemurafenib, Roche) and Tafinlar (dabrafenib, GSK) get FDA and EMA approval for advanced metastatic melanoma. Several follow up BRAF inhibitors are in clinical development by rival pharma  companies  (Novartis, BMS, J&J, Teva) to get a share of expanding melanoma market and improve complete response rates and overcome resistance. Nexavar (sorafenib, Bayer) for for liver (HCC) and renal (RCC) cancer was the first approved and marketed BRAF inhibitor.
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Metastatic Melanoma Cells: Image Details - NCI Visuals Online

Metastatic Melanoma Cells: Image Details - NCI Visuals Online | Melanoma BRAF Inhibitors Review | Scoop.it
Image information and view/download options.
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Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach | Jour...

Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach | Jour... | Melanoma BRAF Inhibitors Review | Scoop.it
Co-occurrence of KRAS mutation and LKB1 loss in NSCLC cells induced an enhanced metabolic activity mirrored by a growth rate vulnerability under limited nutrient conditions relative to cells with the single oncogenetic lesions. Our results hint at the possibility that energy stress induced by calorie restriction regimens may sensitize NSCLCs with these co-occurring lesions to cytotoxic chemotherapy.
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The depth of mutational agony and the exuberance of tumoral T cell ecstasy predict checkpoint salvation

The depth of mutational agony and the exuberance of tumoral T cell ecstasy predict checkpoint salvation | Melanoma BRAF Inhibitors Review | Scoop.it
Genomic biomarkers will help to elucidate which cancer patients will benefit from PD-1 blockade immunotherapy.
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Tolerance and efficacy of BRAF plus MEK inhibition in patients with melanoma who previously have received programmed cell death protein 1‐based therapy - Saab - - Cancer - Wiley Online Library

Tolerance and efficacy of BRAF plus MEK inhibition in patients with melanoma who previously have received programmed cell death protein 1‐based therapy - Saab - - Cancer - Wiley Online Library | Melanoma BRAF Inhibitors Review | Scoop.it
Background Combined BRAF and MEK inhibition (BRAF‐MEK) is a standard therapy for patients with BRAF V600–mutant melanoma, but to the authors’ knowledge, the tolerance, adverse event (AE) profile, and efficacy have not been well defined in the post–programmed cell death protein 1 (PD‐1) setting. Methods Patients with BRAF V600–mutant melanoma who received combined BRAF‐MEK after prior PD‐1–based therapy were assembled from 4 tertiary care centers in the United States and Australia. Dose modification was defined as a treatment break, dose reduction, or intermittent dosing. Rates of hospitalization and discontinuation due to AEs were collected, and overall survival (OS) was calculated using Kaplan‐Meier methods from the time of the initiation of BRAF‐MEK therapy. Results A total of 78 patients were identified as having received a BRAF‐MEK regimen at a median of 34 days after the last dose of PD‐1–based therapy. The majority of patients (86%) received the combination of dabrafenib and trametinib. Approximately 80% of patients had American Joint Committee on Cancer M1c or M1d disease. Sixty‐five regimens (83%) had ≥1 dose modification. The median time to the first dose modification was 14 days; 86% occurred within 90 days and 71% involved pyrexia. Dose modifications were more common in patients receiving BRAF‐MEK <90 days after the last dose of PD‐1 and who were not receiving steroids. Of the dose modifications, 25 (31%) led to an AE‐related hospitalization. Among 55 BRAF‐naive patients, the median time receiving BRAF‐MEK therapy was 5.8 months and the median OS was 15.6 months. Conclusions The majority of patients receiving BRAF‐MEK inhibition after PD‐1 therapy require dose interruptions, and a significant minority require hospitalization for AEs. In this higher risk population, the median time receiving therapy and OS may be inferior to those presented in published phase 3 trials.
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Paper: Safety and Efficacy Data for Combined Checkpoint Inhibition with Ipilimumab (Ipi) and Nivolumab (Nivo) As Consolidation Following Autologous Stem Cell Transplantation (ASCT) for High-Risk He...

Paper: Safety and Efficacy Data for Combined Checkpoint Inhibition with Ipilimumab (Ipi) and Nivolumab (Nivo) As Consolidation Following Autologous Stem Cell Transplantation (ASCT) for High-Risk He... | Melanoma BRAF Inhibitors Review | Scoop.it
Rationale: ASCT remains a standard-of-care as consolidation or salvage for multiple myeloma (MM), post-salvage consolidation for Diffuse Large B-Cell Lymphoma (DLBCL) and upfront consolidation or salvage for Peripheral T-Cell Lymphomas (PTCL) Pts with high-risk disease still show poor outcome and frequent progression within the first 18 months. Maintenance strategies post ASCT, particularly in lymphomas, have failed to show benefit, underlining the need for novel approaches to help disease control following ASCT. We have previously reported on the preliminary safety and efficacy of checkpoint inhibitor consolidation with Ipi and Nivo following ASCT trying to take advantage of the immunological milieu during post-ASCT recovery (Skarbnik et al., ASH 2017). Here we present updated data from our Phase I CPIT-001 trial. Methods: Pts with high-risk DLBCL, PTCL or MM (as defined in Table 1, divided in cohorts) were eligible if they experienced at least stable disease after most recent salvage therapy (NHL, PTCL or relapsed MM) or after induction therapy for high-risk MM. Pts were enrolled prior to ASCT, starting in July 2016. All pts with DLBCL/PTCL received BEAM (carmustine 300 mg/m2 day -6, etoposide 200 mg/m2 and cytarabine 200 mg/m2 days -5 to -2, melphalan 140 mg/m2 day -1) as conditioning regimen for ASCT, all pts with MM received melphalan 200 mg/m2 on day -1 For pts who achieved appropriate hematologic recovery (ANC >800/mm3 and platelets > 20,000/mm3), Ipi/Nivo were started between days 14 and 28 post ASCT. The infusion schedule was: Ipi: 1 mg/kg; 6 doses Weeks 1, 4, 7, 10, 16, 22 Nivo: 3 mg/kg; 12 doses Weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26 Primary objectives were: Safety profile evaluation; PFS and OS at 18 months (PFS18 and OS18). Cox proportional hazards regression was utilized to determine predictors of outcome. Results: 31 pts received at least one dose of Ipi/Nivo following ASCT and were included in the intent-to-treat population. Median follow up for the whole cohort is 16 months. As of February 2018, the FDA has halted all studies including checkpoint inhibitors for pts with MM. At that time, only one pt with MM was actively receiving Ipi/Nivo, which was then discontinued. At 18 months post ASCT, estimated PFS for the entire cohort was 67% and OS was 84% (Figures 1 and 2). Disease-specific PFS18 and OS18 are described in Table 2. At study entry, 48% of pts were in CR (NHLs) or stringent CR (sCR, MMs). At most recent follow-up (range 2-25 months) 71% of pts were in CR (NHL) or sCR (MM). Disease status at study entry (i.e. CR vs <CR) didn’t correlate with PFS nor OS. 65% of pts developed immune-related adverse events (irAEs) grade 2 or higher, requiring treatment with systemic steroids. Most common irAEs of any grade were: colitis (58%), rash (48%), thrombocytopenia (45%), anemia (45%) and transaminitis (32%). One pt (3%) died from complications of pneumonitis related to study drugs. All other irAEs resolved. Median time from 1st Ipi/Nivo to development of irAEs was 4 weeks. Median time to improvement to Grade 1 or baseline was 1 week after high-dose steroids were initiated. Treatment-related AEs of any grade that led to discontinuation of Ipi/Nivo occurred in 6 pts (19%). Development of irAEs, use of steroids or length of steroid-exposure did not correlate with PFS or OS. Conclusion: At 18 months post-ASCT, PFS for pts with high-risk hematological malignancies is 67%. This number underscores the potential for longer remissions by associating checkpoint inhibition with ASCT. For patients in the transplant-naïve MM with high-risk cytogenetics cohort, the 71% PFS18 (fig 3) is particularly striking, when compared to median PFS of 13-15 months in previous reports of ASCT alone in this patient population (Sonneveld et al, Blood 2016). In addition, the primary-refractory DLBCL population (43% of which were not in CR at time of ASCT) presented with a PFS18 of 83% (fig 4), while the reported PFS18 for this patient population with ASCT alone is 50% (Crump et al, Blood 2017). The cohort of pts with DLBCL relapsed within 1 year of induction had the poorest outcomes, possibly related to these pts being the most heavily pretreated in the whole cohort (median of 3 prior lines of therapy), with 57% of pts in this cohort refractory to most recent line of therapy. The manageable toxicity profile, coupled with the encouraging efficacy outcomes warrant further evaluation of this approach in a Phase II trial, which is currently planned.
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The potential role of adenosine signaling in the pathogenesis of melanoma - ScienceDirect

The potential role of adenosine signaling in the pathogenesis of melanoma - ScienceDirect | Melanoma BRAF Inhibitors Review | Scoop.it
bstract
Melanoma cancer cell proliferation, motility, invasion, and tumor growth is affected by the adenosine pathway that consists of adenosine-synthesizing enzymes, receptors, and their respective agonists/antagonists. Accumulating evidence suggests that ischemia and inflammation, two conditions associated with melanoma, display dysregulated adenosine metabolism, which implicates it as the mechanism responsible for the pathogenesis of melanoma, thereby resulting in advanced diagnosis and therapy. Suppression of adenosine signaling by inhibiting adenosine receptors or adenosine-generating enzymes (CD39 and CD73) on melanoma cells presents a novel therapeutic target for patients with melanoma. This review summarizes the role of adenosine signaling in the pathogenesis of melanoma to advance its understanding and hence improve therapeutics and management.
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Nivolumab for adjuvant treatment of resected stage III and IV melanoma [ID1316] | Guidance and guidelines | NICE

Nivolumab for adjuvant treatment of resected stage III and IV melanoma [ID1316] | Guidance and guidelines | NICE | Melanoma BRAF Inhibitors Review | Scoop.it
Nivolumab for adjuvant treatment of resected stage III and IV melanoma [ID1316]...
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Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma

Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma | Melanoma BRAF Inhibitors Review | Scoop.it
Mucosal melanoma is a rare, but deadly, form of melanoma that occurs in sun-protected tissues. Little is known about the genetic alterations that drive the growth of these tumors. Ablain et al. sequenced mucosal melanomas from 43 patients and found that a substantial fraction showed inactivation or loss of SPRED1 , a gene that encodes a negative regulator of RAS–MAPK (mitogen-activated protein kinase) signaling. Using a platform called MAZERATI (Modeling Approach in Zebrafish for Rapid Tumor Initiation), they discovered that SPRED1 loss may help explain the poor response of melanoma patients to drugs that inhibit the KIT tyrosine kinase. The results suggest that a combination of KIT inhibitors and drugs that inhibit MAPK signaling may be more effective.

Science , this issue p. [1055][1]

Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. These findings provide a rationale for MAPK inhibition in SPRED1-deficient melanomas and introduce a zebrafish modeling approach that can be used more generally to dissect genetic interactions in cancer.

[1]: /lookup/doi/10.1126/science.aau6509
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Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK s

Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK s | Melanoma BRAF Inhibitors Review | Scoop.it
Highlights

Blocking NKG2A unleashes both T and NK cell effector functions

Combined blocking of the NKG2A and the PD-1 axis promotes anti-tumor immunity

Blocking NKG2A and triggering CD16 illustrates the efficacy of dual checkpoint therapy
Summary
Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.
Graphical Abstract
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Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results | Journ...

Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results | Journ... | Melanoma BRAF Inhibitors Review | Scoop.it
AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on...
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Early Use of Systemic Corticosteroids in Patients with Advanced NSCLC Treated with Nivolumab

Early Use of Systemic Corticosteroids in Patients with Advanced NSCLC Treated with Nivolumab | Melanoma BRAF Inhibitors Review | Scoop.it
Checkpoint inhibitors augment the immune system’s natural surveillance mechanisms
and have increasing applications in NSCLC. Immunosuppressive corticosteroids are also
frequently used in this population to treat unwanted inflammation.
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The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention

The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention | Melanoma BRAF Inhibitors Review | Scoop.it

Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma.

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High response rate to PD-1 blockade in desmoplastic melanomas

High response rate to PD-1 blockade in desmoplastic melanomas | Melanoma BRAF Inhibitors Review | Scoop.it
Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, but is highly associated with ultraviolet light DNA damage.[] We analysed 60 patients ...
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JCI - Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity

JCI - Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity | Melanoma BRAF Inhibitors Review | Scoop.it

While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte–associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4–binding domain. Upon reaching the tumor, the outer domain was cleaved by membrane type-serine protease 1 (MT-SP1) present in the tumor microenvironment, leading to enhanced localization of CTLA4 blockade. Anti-CTLA4 DVD markedly reduced multiorgan immune toxicity by preserving tissue-resident Tregs in Rag 1–/– mice that received naive donor CD4+ T cells from WT C57BL/6j mice. Moreover, anti-CTLA4 DVD induced potent antitumor effects by decreasing tumor-infiltrating Tregs and increasing the infiltration of antigen-specific CD8+ T lymphocytes in TRAMP-C2–bearing C57BL/6j mice. Treg depletion was mediated through the antibody-dependent cellular cytotoxicity (ADCC) mechanism, as anti-CTLA4 without the FcγR-binding portion (anti-CTLA4 DANA) spared Tregs, preventing treatment-induced toxicities. In summary, our results demonstrate an approach to anti-CTLA4 blockade that depletes tumor-infiltrating, but not tissue-resident, Tregs, preserving antitumor effects while minimizing toxicity. Thus, our tumor-conditional anti-CTLA4 DVD provides an avenue for uncoupling antitumor efficacy from immunotherapy-induced toxicities.

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Frontiers | Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma | Immunology

Frontiers | Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma | Immunology | Melanoma BRAF Inhibitors Review | Scoop.it
The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively. In MM it seems that an approach based on combination treatment might be appropriate as unsatisfactory results have been yielded by monotherapy with PD-1/PD-L1 inhibitors. Immunomodulatory drugs, which are the current cornerstone of MM treatment, are the most logical partners as they possess many possibly synergistic effects. Nevertheless, the initially optimistic results have become disappointing due to the excessive and unpredictable toxicity of the combination of pembrolizumab with lenalidomide or pomalidomide. The FDA has suspended or put on hold several phase 3 trials in relapsed as well as in newly diagnosed myeloma patients. There are also other potentially synergistic and promising combinations, such as the anti-CD38 monoclonal antibody daratumumab, irradiation, etc. Not only the effective partner but also the correct timing of the initiation of the PD-1/PD-L1 inhibitors treatment seems to be of utmost importance. These strategies are currently being examined in various stages of myeloma such as during consolidation post autologous stem cell transplantation, targeting minimal residual disease or even in high risk smoldering myeloma.

Introduction
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Nanoparticle-Mediated Remodeling of the Tumor Microenvironment to Enhance Immunotherapy - ACS Nano (ACS Publications)

Nanoparticle-Mediated Remodeling of the Tumor Microenvironment to Enhance Immunotherapy - ACS Nano (ACS Publications) | Melanoma BRAF Inhibitors Review | Scoop.it
Nanoscience has long been lauded as a method through which tumor-associated barriers could be overcome. As successful as cancer immunotherapy has been, limitations associated with the tumor microenvironment or side effects of systemic treatment have become more apparent. In this Review, we seek to lay out the therapeutic challenges associated with the tumor microenvironment and the ways in which nanoscience is being applied to remodel the tumor microenvironment and increase the susceptibility of many cancer types to immunotherapy. We detail the nanomedicines on the cutting edge of cancer immunotherapy and how their interactions with the tumor microenvironment make them more effective than systemically administered immunotherapies.

Keywords: cancer; checkpoint inhibitors; cytokines; cytotoxic T cells; immunogenic cell death; immunotherapy; nanoparticles; nanovaccine; tumor microenvironment
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Intralesional PV‐10 for the treatment of in‐transit melanoma metastases—Results of a prospective, non‐randomized, single center study - Read - 2018 - Journal of Surgical Oncology - Wiley Online Lib...

Intralesional PV‐10 for the treatment of in‐transit melanoma metastases—Results of a prospective, non‐randomized, single center study - Read - 2018 - Journal of Surgical Oncology - Wiley Online Lib... | Melanoma BRAF Inhibitors Review | Scoop.it
Abstract Background Patients with in‐transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi‐center study, PV‐10 treatment was continued at our institution for patients with in‐transit disease. Methodology An open‐label, non‐randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV‐10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions. Results Forty‐five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV‐10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow‐up duration was 22 months and the median overall survival was 25 months from first PV‐10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03).

 

Conclusions Intralesional PV‐10 provided rapid lesion‐specific ablation of melanoma metastases with well‐tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume. 1

 

 

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The potential role of adenosine signaling in the pathogenesis of melanoma - ScienceDirect

The potential role of adenosine signaling in the pathogenesis of melanoma - ScienceDirect | Melanoma BRAF Inhibitors Review | Scoop.it
bstract
Melanoma cancer cell proliferation, motility, invasion, and tumor growth is affected by the adenosine pathway that consists of adenosine-synthesizing enzymes, receptors, and their respective agonists/antagonists. Accumulating evidence suggests that ischemia and inflammation, two conditions associated with melanoma, display dysregulated adenosine metabolism, which implicates it as the mechanism responsible for the pathogenesis of melanoma, thereby resulting in advanced diagnosis and therapy. Suppression of adenosine signaling by inhibiting adenosine receptors or adenosine-generating enzymes (CD39 and CD73) on melanoma cells presents a novel therapeutic target for patients with melanoma. This review summarizes the role of adenosine signaling in the pathogenesis of melanoma to advance its understanding and hence improve therapeutics and management.
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MicroRNA-sequencing data analyzing melanoma development and progression - ScienceDirect

MicroRNA-sequencing data analyzing melanoma development and progression - ScienceDirect | Melanoma BRAF Inhibitors Review | Scoop.it
Highlights

RNA-Seq revealed 1367 miRNAs as differentially regulated in melanoma.


Approximately half of the dysregulated miRNAs show induction of expression.


The obtained data compromises several differences compared to existing cDNA arrays.


Many of the regulated miRNAs are not yet described as melanoma-associated.
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Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial - Scienc...

Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial - Scienc... | Melanoma BRAF Inhibitors Review | Scoop.it
Highlights

Response rates were higher with pembrolizumab than with ipilimumab, regardless of line of therapy.


Response rates were higher with pembrolizumab irrespective of tumour programmed death ligand 1 (PD-L1) expression.


Survival was superior with pembrolizumab in PD-L1–positive tumours and comparable to ipilimumab in PD-L1–negative tumours.


Findings support pembrolizumab use with advanced melanoma, regardless of line of prior therapy or PD-L1 status.
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Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model

Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model | Melanoma BRAF Inhibitors Review | Scoop.it
Adoptive cell transfer (ACT) is a promising cancer immunotherapy that involves isolating T cells from cancer patients that are capable of targeting their tumor, selecting the more active T cells and expanding those in the ...
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Nivolumab/Ipilimumab Combo Misses Primary Endpoint in Phase III SCLC Trial

Nivolumab/Ipilimumab Combo Misses Primary Endpoint in Phase III SCLC Trial | Melanoma BRAF Inhibitors Review | Scoop.it
The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) did not improve overall survival versus placebo as a maintenance therapy for patients with extensive-stage small cell lung cancer&nbsp;without disease progression following frontline platinum-based chemotherapy.&nbsp;...
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A biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis

A biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis | Melanoma BRAF Inhibitors Review | Scoop.it
Photodynamic therapy is usually ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Here, the authors design a biomimetic nanoreactor which can convert nutriment glucose into toxic singlet oxygen via chemiluminescence resonance energy transfer with...
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Melanoma Associated Antigen (PNL2) Mouse Monoclonal Antibody

Melanoma Associated Antigen (PNL2) Mouse Monoclonal Antibody | Melanoma BRAF Inhibitors Review | Scoop.it
Melanoma Associated Antigen (PNL2) Mouse Monoclonal Antibody, one of over 250 optimized pre-diluted reagents for use on the BenchMark IHC/ISH automated slide staining instruments by Ventana Medical Systems, Inc.
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Fine-tuning cell death: new component of death machinery revealed

Fine-tuning cell death: new component of death machinery revealed | Melanoma BRAF Inhibitors Review | Scoop.it
An important component of the microscopic machinery that drives cell death has been identified by Walter and Eliza Hall Institute scientists.
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The Study of Brain Tumor Stem Cell Invasion

The Study of Brain Tumor Stem Cell Invasion | Melanoma BRAF Inhibitors Review | Scoop.it
bstract
Ninety percent of deaths from solid tumors have been ascribed to the invasion and metastatic dissemination of cancer cells. One of the most fundamental prerequisites of brain tumor stem cell invasion is their ability to penetrate and traverse through the basement membrane and stromal compartments displacing from their original point of origin and repopulating at a distant site and adjacent tissue. In order to propose a successful clinical strategy, the investigation of the molecular determinants of invasion must factor in measurements and predictors of the complexity of brain tumor invasion potential accounting for the physiological scenarios encountered in the tumor niche. This chapter will highlight some laboratory approaches such as: spot assay, 3D chemogradient chambers, Fluoroblok™ tumor invasion, organotypics, and 3D tumor spheroid assays that could help mitigate the investigation of a tumor stem cell’s invasion capacity through restrictive 3D environments otherwise seen in vivo.

Key words
Motility BTICs Invasive capacity 
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