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Targeted therapy, immunotherapy

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https://www.readbyqxmd.com/read/29331888/a-longitudinal-analysis-of-ido-and-pdl1-expression-during-immune-or-targeted-therapy-in-advanced-melanoma
#1
Lukas Krähenbühl, Simone M Goldinger, Joanna Mangana, Katrin Kerl, Ines Chevolet, Liève Brochez, Christine Horak, Mitch Levesque, Reinhard Dummer, Phil F Cheng
A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#2
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#3
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#4
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29329208/advances-in-molecular-profiling-and-categorisation-of-pancreatic-adenocarcinoma-and-the-implications-for-therapy
#5
REVIEW
Rille Pihlak, Jamie M J Weaver, Juan W Valle, Mairéad G McNamara
Pancreatic ductal adenocarcinoma (PDAC) continues to be a disease with poor outcomes and short-lived treatment responses. New information is emerging from genome sequencing identifying potential subgroups based on somatic and germline mutations. A variety of different mutations and mutational signatures have been identified; the driver mutation in around 93% of PDAC is KRAS, with other recorded alterations being SMAD4 and CDKN2A. Mutations in the deoxyribonucleic acid (DNA) damage repair pathway have also been investigated in PDAC and multiple clinical trials are ongoing with DNA-damaging agents...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29329202/epcam-immunotherapy-versus-specific-targeted-delivery-of-drugs
#6
REVIEW
Joanna Macdonald, Justin Henri, Kislay Roy, Emma Hays, Michelle Bauer, Rakesh Naduvile Veedu, Normand Pouliot, Sarah Shigdar
The epithelial cell adhesion molecule (EpCAM), or CD326, was one of the first cancer associated biomarkers to be discovered. In the last forty years, this biomarker has been investigated for use in personalized cancer therapy, with the first monoclonal antibody, edrecolomab, being trialled in humans more than thirty years ago. Since then, several other monoclonal antibodies have been raised to EpCAM and tested in clinical trials. However, while monoclonal antibody therapy has been investigated against EpCAM for almost 40 years as primary or adjuvant therapy, it has not shown as much promise as initially heralded...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#7
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
January 10, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29329112/master-protocols-in-lung-cancer-experience-from-lung-master-protocol
#8
Vincent K Lam, Vassiliki Papadimitrakopoulou
PURPOSE OF REVIEW: Contemporary advances in the understanding of the molecular and immunologic basis of metastatic lung cancer have firmly changed its treatment paradigm to a personalized, biomarker-driven approach. However, the majority of lung-cancer patients [especially lung squamous cell carcinoma (LUSC)] still do not have effective targeted therapeutic options. Master protocols, such as Lung-MAP, represent an innovative clinical trial approach designed to accelerate evaluation of novel biomarker-driven therapies...
January 10, 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29329051/non-genetic-engineering-of-cytotoxic-t-cells-to-target-il-4-receptor-enhances-tumor-homing-and-therapeutic-efficacy-against-melanoma
#9
Gowri Rangaswamy Gunassekaran, Chae-Moon Hong, Sri Murugan Poongkavithai Vadevoo, Lianhua Chi, Padmanaban Guruprasath, Byung-Cheol Ahn, Ha-Jeong Kim, Tae Heung Kang, Byungheon Lee
Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine...
January 8, 2018: Biomaterials
https://www.readbyqxmd.com/read/29327613/potential-immunotherapies-for-sarcoidosis
#10
Van Le, Elliott D Crouser
Sarcoidosis is a chronic granulomatous inflammatory disease that commonly causes lung disease, but can affect other vital organs and tissues. The cause of sarcoidosis is unknown, and current therapies are commonly limited by lack of efficacy, adverse side effects, and excessive cost. Areas covered: The manuscript will provide a review of current concepts relating to the pathogenesis of sarcoidosis, and how these disease mechanisms may be leveraged to develop more effective treatments for sarcoidosis. It provides only a brief summary of currently accepted therapy, while focusing more extensively on potential novel therapies...
January 12, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29326816/immune-checkpoint-inhibition-prospects-for-prevention-and-therapy-of-hepatocellular-carcinoma
#11
REVIEW
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#12
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29325434/collection-of-real-world-data-on-nivolumab-s-effectiveness-in-renal-cell-carcinoma-rationale-for-an-observational-study
#13
Jens Bedke, Marc-Oliver Grimm, Viktor Grünwald
Renal cell carcinoma (RCC) represents the seventh (men) respectively tenth (women) most frequent cancer in western countries. After one or more lines of VEGF-targeted therapy, immunotherapy with nivolumab is strongly recommended in patients with metastatic RCC. Nivolumab is the first, and so far, only approved programmed death 1 (PD-1) immune checkpoint inhibitor to demonstrate a gain in overall survival in RCC. We describe herein design and rationale of trial CA209653 ('NIS NORA'), a prospective, noninterventional cohort study investigating the effectiveness of nivolumab...
January 12, 2018: Future Oncology
https://www.readbyqxmd.com/read/29323537/investigational-therapies-targeting-cd37-for-the-treatment-of-b-cell-lymphoid-malignancies
#14
Magdalena Witkowska, Piotr Smolewski, Tadeusz Robak
While chemotherapy still remains a cornerstone of oncologic therapy, immunotherapy with monoclonal antibodies has steadily improved the treatment strategy for several hematologic malignancies. New treatment options need to be developed for relapsed and refractory non-Hodgkin lymphoma (NHL) patients. Currently, novel agents targeting specific molecules on the surface of lymphoma cells, such as anti-CD37 antibodies, are under considerable investigation. Here we report on anti-CD37 targeting for the treatment of patients with B-cell NHL...
January 11, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29322476/negative-regulators-of-cell-death-pathways-in-cancer-perspective-on-biomarkers-and-targeted-therapies
#15
REVIEW
Ali Razaghi, Kirsten Heimann, Patrick M Schaeffer, Spencer B Gibson
Cancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge...
January 10, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29317100/-practices-in-infectious-pathology-in-france-in-2015-results-of-the-national-survey
#16
Arnault Tauziède-Espariat, Fabrice Chrétien, Grégory Jouvion, Homa Alde-Biassette, Paul Hofman
Pathologists have been, are and will be always implicated in the diagnosis of infectious and tropical diseases. The resurgence of opportunistic infections due to the development of immunosuppressive drugs, the increase of migratory involvements draining tropical infections and the last epidemics spotlight the importance of pathologists in the field of infectious diseases. However, cancer is nowadays the first preoccupation of pathologists, which is constantly subject to evaluate diagnostic and prognostic markers and factors predictive to targeted therapy response or immunotherapy...
January 6, 2018: Annales de Pathologie
https://www.readbyqxmd.com/read/29315242/nf-kappab-two-sides-of-the-same-coin
#17
REVIEW
Bruno R B Pires, Rafael C M C Silva, Gerson M Ferreira, Eliana Abdelhay
Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies...
January 9, 2018: Genes
https://www.readbyqxmd.com/read/29313975/near-infrared-photoimmunotherapy-targeting-egfr-shedding-new-light-on-glioblastoma-treatment
#18
Thomas A Burley, Justyna Mączyńska, Anant Shah, Wojciech Szopa, Kevin J Harrington, Jessica K R Boult, Anna Mrozek-Wilczkiewicz, Maria Vinci, Jeffrey C Bamber, Wojciech Kaspera, Gabriela Kramer-Marek
Glioblastomas (GBM) are high-grade brain tumours, differentially driven by alterations (amplification, deletion, or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signalling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy...
January 5, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29313655/lung-cancer-management
#19
Timothy F Mott
Lung cancer management that is individualized for age, comorbidities, cancer type, cancer stage, and patient preference has long been a cornerstone of management. New to this realm of individualized management are the emerging biologic therapies, immunotherapies, and targeted therapies for non-small-cell lung cancer provided by advances in genetics and molecular medicine. These techniques have led to a new field of precision medicine based on the unique molecular characteristics of a specific patient and the specific cancer...
January 2018: FP Essentials
https://www.readbyqxmd.com/read/29312597/targeting-of-cd122-enhances-antitumor-immunity-by-altering-the-tumor-immune-environment
#20
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
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