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https://www.readbyqxmd.com/read/28447210/mitf-suppression-by-ch5552074-inhibits-cell-growth-in-melanoma-cells
#1
Satoshi Aida, Yukiko Sonobe, Munehiro Yuhki, Kiyoaki Sakata, Toshihiko Fujii, Hiroshi Sakamoto, Takakazu Mizuno
PURPOSE: Although treatment of melanoma with BRAF inhibitors and immune checkpoint inhibitors achieves a high response rate, a subset of melanoma patients with intrinsic and acquired resistance are insensitive to these therapeutics, so to improve melanoma therapy other target molecules need to be found. Here, we screened our chemical library to identify an anti-melanoma agent and examined its action mechanisms to show cell growth inhibition activity. METHODS: We screened a chemical library against multiple skin cancer cell lines and conducted ingenuity pathway analysis (IPA) to investigate the mechanisms of CH5552074 activity...
April 26, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28447005/future-directions-in-esophageal-cancer-therapy
#2
Ori Wald, Brandon Smaglo, Henry Mok, Shawn S Groth
Resection techniques for esophageal carcinoma continue to evolve, from endoscopic mucosal resection or endoscopic submucosal dissection for early stage disease to standard and robot-assisted minimally invasive esophagectomy as part of multimodal therapy for locally advanced disease. Though currently limited to assessing conduit perfusion and sentinel lymph nodes, embedded technology in the robotic surgical platform will likely play an expanded role during esophagectomy in the future. The use of targeted therapies, checkpoint inhibitors, engineered immune cell therapy, and cancer vaccines show promise in the treatment of systemic disease...
March 2017: Annals of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/28446466/landscape-of-combination-immunotherapy-and-targeted-therapy-to-improve-cancer-management
#3
Leandro M Colli, Mitchell J Machiela, Han Zhang, Timothy Myers, Lea Jessop, Olivier Delattre, Kai Yu, Stephen J Chanock
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic data sets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide non-synonymous mutations (NsM) that exceeds a proposed threshold for response to checkpoint inhibitors...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28444424/the-experience-of-immune-checkpoint-inhibitors-in-chinese-patients-with-metastatic-melanoma-a-retrospective-case-series
#4
Xizhi Wen, Ya Ding, Jingjing Li, Jingjing Zhao, Ruiqing Peng, Dandan Li, Baoyan Zhu, Yao Wang, Xing Zhang, Xiaoshi Zhang
Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively...
April 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28443099/a-century-of-radiation-therapy-and-adaptive-immunity
#5
REVIEW
Dörthe Schaue
The coming of age for immunotherapy (IT) as a genuine treatment option for cancer patients through the development of new and effective agents, in particular immune checkpoint inhibitors, has led to a huge renaissance of an old idea, namely to harness the power of the immune system to that of radiation therapy (RT). It is not an overstatement to say that the combination of RT with IT has provided a new conceptual platform that has re-energized the field of radiation oncology as a whole. One only has to look at the immense rise in sessions at professional conferences and in grant applications dealing with this topic to see its emergence as a force, while the number of published reviews on the topic is staggering...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28442918/targeting-the-pd-1-pathway-in-pediatric-solid-tumors-and-brain-tumors
#6
REVIEW
Lars M Wagner, Val R Adams
While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442891/spotlight-on-nivolumab-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#7
REVIEW
Vyshak Alva Venur, Monika Joshi, Kenneth G Nepple, Yousef Zakharia
Several tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors and molecules inhibiting the mammalian target of rapamycin are being used for management of metastatic renal cell carcinoma (mRCC); however, there is still a potential for improvement. Immune checkpoint inhibitors like nivolumab and other PD-1/PD-L1 inhibitors provide an alternative approach for patients with mRCC. In this article, the authors review the safety profile and outcomes of phase 1, 2, and 3 clinical trials of nivolumab in mRCC...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28441372/assessing-response-of-high-grade-gliomas-to-immune-checkpoint-inhibitors
#8
Solmaz Sahebjam, Dexter G Stallworth, Sepideh Mokhtari, Nam D Tran, John A Arrington
BACKGROUND: Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases. METHODS: This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28439495/immunotherapies-in-sarcoma-updates-and-future-perspectives
#9
REVIEW
Marwan Ghosn, Elie El Rassy, Hampig Raphael Kourie
Sarcomas are malignant tumors that are characterized by a wide diversity of subtypes with various cytogenetic profiles. Despite major treatment breakthroughs, standard treatment modalities combining chemotherapy, radiotherapy, and surgery failed to improve overall survival. Therefore, high expectations are foreseen with immunotherapy upon its maturation and better understanding of its mechanism of action. This paper presents a targeted review of the published data and ongoing clinical trials in immunotherapies of sarcomas, mainly adoptive cell therapies, cancer vaccines and immune checkpoint inhibitors...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28438889/fda-approval-summary-nivolumab-for-the-treatment-of-relapsed-or-progressive-classical-hodgkin-lymphoma
#10
Yvette L Kasamon, R Angelo de Claro, Yaping Wang, Yuan Li Shen, Ann T Farrell, Richard Pazdur
On May 17, 2016, after an expedited priority review, the U.S. Food and Drug Administration granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (BV). Nivolumab in cHL had been granted breakthrough therapy designation. Accelerated approval was based on two single-arm, multicenter trials in adults with cHL. In 95 patients with relapsed or progressive cHL after autologous HSCT and post-transplantation BV, nivolumab, dosed at 3 mg/kg intravenously every 2 weeks, produced a 65% (95% confidence interval: 55%-75%) objective response rate (58% partial remission, 7% complete remission)...
April 24, 2017: Oncologist
https://www.readbyqxmd.com/read/28436601/management-of-skin-adverse-events-associated-with-immune-checkpoint-inhibitors-in-patients-with-melanoma-a-nursing-perspective
#11
Melissa Thebeau, Krista Rubin, Matthias Hofmann, Julia Grimm, Alyona Weinstein, Jennifer N Choi
PURPOSE: Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies...
April 24, 2017: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#12
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#13
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#14
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28434510/pd-l1-testing-for-immune-checkpoint-inhibitors-in-mesothelioma-for-want-of-anything-better
#15
EDITORIAL
Sylvie Lantuejoul, Nolwenn Le Stang, Francesca Damiola, Arnaud Scherpereel, Francoise Galateau-Sallé
No abstract text is available yet for this article.
May 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#16
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434398/the-use-of-immunotherapy-in-the-treatment-of-melanoma
#17
REVIEW
Tala Achkar, Ahmad A Tarhini
Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully overcomes this tumor-mediated immune suppression has made the greatest impact in the management of this disease over the past few years. This progress through immunotherapy builds upon earlier successes that interferon-α had in the treatment of melanoma in the adjuvant setting, as well as that of high-dose interleukin-2 in advanced melanoma...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28433197/-what-is-the-place-of-the-combinations-for-immunotherapy-with-chemotherapy-or-with-other-immune-checkpoint-inhibitors
#18
REVIEW
Gaëlle Douchet, Sandrine Aspeslagh
Immune checkpoint blockade by the use of anti-PD(L)1 or anti-CTLA4 antibodies can induce long lasting disease response and maybe cure in a lot of advanced cancer patients. This ongoing immunotherapy revolution has given new hope to cancer patients and oncologists. However, still the majority of cancer patients do not respond to immune checkpoint blockade and novel therapeutical possibilities are being tested in several clinical trials. One of the possibilities to enhance responses to immune checkpoint blockade is the combination with chemotherapy or with other immune checkpoint blockade molecules...
April 19, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#19
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28431920/the-microbiome-in-anti-cancer-therapy
#20
REVIEW
Stavros Bashiardes, Timur Tuganbaev, Sara Federici, Eran Elinav
The commensal microbiome constitutes an important modulator of host physiology and risk of disease, including cancer development and progression. Lately, the microbiome has been suggested to modulate the efficacy of anti-cancer treatment. Examples include chemotherapy and total body irradiation-induced barrier function disruption, leading to microbial efflux that drives activation of anti-tumorigenic T cells; Microbiome-driven release of reactive oxygen species contributing to the efficacy of platinum salts; and microbiome-induced immune priming promoting the anti-tumor effects of alkylating chemotherapy and immune checkpoint inhibitors...
April 18, 2017: Seminars in Immunology
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