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https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#1
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#2
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537531/clinical-features-of-nivolumab-induced-thyroiditis-a-case-series-study
#3
Ichiro Yamauchi, Yoriko Sakane, Yorihide Fukuda, Toshihito Fujii, Daisuke Taura, Masakazu Hirata, Keisho Hirota, Yohei Ueda, Yugo Kanai, Yui Yamashita, Eri Kondo, Masakatsu Sone, Akihiro Yasoda, Nobuya Inagaki
BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international phase 3 studies and national postmarketing surveillance of nivolumab in Japan...
May 24, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#4
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28524161/efficacy-of-anti-pd-1-therapy-in-patients-with-melanoma-brain-metastases
#5
Sagun Parakh, John J Park, Shehara Mendis, Rajat Rai, Wen Xu, Serigne Lo, Martin Drummond, Catherine Rowe, Annie Wong, Grant McArthur, Andrew Haydon, Miles C Andrews, Jonathan Cebon, Alex Guminski, Richard F Kefford, Georgina V Long, Alexander M Menzies, Oliver Klein, Matteo S Carlino
BACKGROUND: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. METHOD: We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS)...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522738/imaging-of-programmed-death-ligand-1-pd-l1-impact-of-protein-concentration-on-distribution-of-anti-pd-l1-spect-agent-in-an-immunocompetent-melanoma-murine-model
#6
Jessie R Nedrow, Anders Josefsson, Sunju Park, Sagar Ranka, Sanchita Roy, George Sgouros
Programmed cell Death Ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy targeting immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects (irAEs). Recently, we developed an antibody based PD-L1-targeted imaging agent to identify PD-L1 positive tumors in vivo...
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#7
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28508938/immunotherapy-for-the-treatment-of-uveal-melanoma-current-status-and-emerging-therapies
#8
REVIEW
Kimberly M Komatsubara, Richard D Carvajal
PURPOSE OF REVIEW: Uveal melanoma is a distinct subset of melanoma with a biology and treatment approach that is unique from that of cutaneous melanoma. Here we will review the current data evaluating immunotherapies in both the adjuvant and metastatic settings in uveal melanoma. RECENT FINDINGS: In the adjuvant setting, interferon demonstrated no survival benefit in uveal melanoma, and studies evaluating immune-based strategies such as vaccine therapy are ongoing...
July 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28500560/radiation-necrosis-with-stereotactic-radiosurgery-combined-with-ctla-4-blockade-and-pd-1-inhibition-for-treatment-of-intracranial-disease-in-metastatic-melanoma
#9
Penny Fang, Wen Jiang, Pamela Allen, Isabella Glitza, Nandita Guha, Patrick Hwu, Amol Ghia, Jack Phan, Anita Mahajan, Hussein Tawbi, Jing Li
Immune checkpoint inhibitors have demonstrated remarkable benefits in cancer patients. However, concern regarding toxicity in the setting of stereotactic radiosurgery (SRS) is often raised. In this study, we characterize radiation necrosis (RN) following immunotherapy and SRS. Melanoma patients treated with SRS and anti-CTLA-4 and/or anti-PD-1 at our institution from January 2006 to December 2015 were retrospectively reviewed. Overall survival (OS) and time to RN were assessed using Kaplan-Meier analysis. Logistic regression and Cox proportional hazards analyses were performed to identify predictors of radiation necrosis-free survival (RNFS) and RN risk...
May 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#10
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28494868/interferon-receptor-signaling-pathways-regulating-pd-l1-and-pd-l2-expression
#11
Angel Garcia-Diaz, Daniel Sanghoon Shin, Blanca Homet Moreno, Justin Saco, Helena Escuin-Ordinas, Gabriel Abril Rodriguez, Jesse M Zaretsky, Lu Sun, Willy Hugo, Xiaoyan Wang, Giulia Parisi, Cristina Puig Saus, Davis Y Torrejon, Thomas G Graeber, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Robert Damoiseaux, Roger S Lo, Antoni Ribas
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28489616/complete-response-to-anti-pd-1-nivolumab-in-massive-skin-metastasis-from-melanoma-efficacy-and-tolerability-in-an-elderly-patient
#12
Andrea Sponghini, Federica Patrucco, Roberto Giorgione, Pamela Farinelli, Francesca Zottarelli, David Rondonotti, Paola Savoia
The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments...
May 9, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28487385/immune-related-gene-expression-profiling-after-pd-1-blockade-in-non-small-cell-lung-carcinoma-head-and-neck-squamous-cell-carcinoma-and-melanoma
#13
Aleix Prat, Alejandro Navarro, Laia Paré, Noemí Reguart, Patricia Galvan, Tomás Pascual, Alex Martínez, Paolo Nuciforo, Laura Comerma, Llucia Alos, Nuria Pardo, Susana Cedrés, Cheng Fan, Joel S Parker, Lydia Gaba, Ivan Victoria, Nuria Viñolas, Ana Vivancos, Ana Arance, Enriqueta Felip
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor speciments from 65 patients with melanoma, lung non-squamous, squamous cell lung or head and neck cancers who were treated with the approved PD1 targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS)...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28480561/immunotherapy-induced-sarcoidosis-in-patients-with-melanoma-treated-with-pd-1-checkpoint-inhibitors-case-series-and-immunophenotypic-analysis
#14
Anna J Lomax, Helen M McGuire, Catriona McNeil, Clara J Choi, Peter Hersey, Deme Karikios, Kerwin Shannon, Sebastian van Hal, Urszula Carr, Anne Crotty, Sandeep K Gupta, Jane Hollingsworth, Haewon Kim, Barbara Fazekas de St Groth, Neil McGill
AIM: Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanoma patients receiving anti-neoplastic therapy. We evaluated a case series of melanoma patients who developed immunotherapy-induced sarcoidosis. METHODS: Three patients with melanoma (n = 1 resected Stage III, n = 2 metastatic) treated with anti-programmed cell death (PD)-1 antibody therapy at two institutions developed biopsy-proven sarcoidosis...
May 8, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28476944/impact-of-age-on-outcomes-with-immunotherapy-for-patients-with-melanoma
#15
Allison S Betof, Ryan D Nipp, Anita Giobbie-Hurder, Romany A N Johnpulle, Krista Rubin, Samuel M Rubinstein, Keith T Flaherty, Donald P Lawrence, Douglas B Johnson, Ryan J Sullivan
BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers. METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28469878/vogt-koyanagi-harada-disease-like-posterior-uveitis-in-the-course-of-nivolumab-anti-pd-1-antibody-interposed-by-vemurafenib-braf-inhibitor-for-metastatic-cutaneous-malignant-melanoma
#16
Toshihiko Matsuo, Osamu Yamasaki
A patient with metastatic cutaneous malignant melanoma developed Vogt-Koyanagi-Harada disease-like posterior uveitis after two nivolumab (anti-PD-1 antibody) injections. Vogt-Koyanagi-Harada disease, with the background of autoimmunity against choroidal melanocytes, suggests nivolumab be working by disintegrating inhibition circuit of T cells against a common epitope shared between melanoma cells and normal melanocytes.
May 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28467964/phase-i-study-of-nivolumab-combined-with-ifn-%C3%AE-for-patients-with-advanced-melanoma
#17
Taku Fujimura, Takanori Hidaka, Yumi Kambayashi, Sadanori Furudate, Aya Kakizaki, Hisayuki Tono, Akira Tsukada, Takahiro Haga, Akira Hashimoto, Ryo Morimoto, Takuhiro Yamaguchi, Tadao Takano, Setsuya Aiba
The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so nivolumab-based combined therapies that enhance anti-tumor immune responses in patients with metastatic melanoma are of great interest to dermato-oncologists. As we have previously reported, IFN-β enhances the anti-tumor immune response of anti-PD-1 antibodies against B16F10 melanoma in vivo. To explore the potential of this property of IFN-β as part of a combination therapy for the treatment of metastatic melanoma patients, we performed a phase 1 trial, using a traditional rule-based 3 + 3 design, on patients with advanced melanoma...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467522/eruptive-keratoacanthomas-associated-with-pembrolizumab-therapy
#18
Azael Freites-Martinez, Bernice Y Kwong, Kerri E Rieger, Daniel G Coit, A Dimitrios Colevas, Mario E Lacouture
Importance: To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab. Objective: To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management. Design, Setting, and Participants: Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs. Interventions: All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery...
May 3, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28464441/current-studies-of-immunotherapy-in-head-and-neck-cancer
#19
Volkan Dogan, Thorsten Rieckmann, Adrian Münscher, Chia-Jung Busch
BACKGROUND: Recently enormous progress in cancer therapy has been achieved by the use of immune checkpoint inhibitors. Activating the body's own immune system has added a novel and powerful therapeutic option for the treatment of melanoma and lung cancer. Furthermore, the potential use of immunotherapy is being extensively explored also in other malignancies. OBJECTIVE OF REVIEW: This review summarizes current clinical studies using immune checkpoint modulators for the treatment of head and neck cancer (HNSCC)...
May 2, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28459947/systemic-inflammatory-reaction-syndrome-during-combined-kinase-inhibitor-therapy-following-anti-pd-1-therapy-for-melanoma
#20
Mirjana Urosevic-Maiwald, Joanna Mangana, Reinhard Dummer
No abstract text is available yet for this article.
April 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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