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https://www.readbyqxmd.com/read/28221865/cost-effectiveness-of-immune-checkpoint-inhibition-in-braf-wild-type-advanced-melanoma
#1
Christine G Kohn, Simon B Zeichner, Qiushi Chen, Alberto J Montero, Daniel A Goldstein, Christopher R Flowers
Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220466/cardiovascular-toxicities-associated-with-cancer-immunotherapies
#2
REVIEW
Daniel Y Wang, Gosife Donald Okoye, Thomas G Neilan, Douglas B Johnson, Javid J Moslehi
PURPOSE OF REVIEW: We review the cardiovascular toxicities associated with cancer immune therapies and discuss the cardiac manifestations, potential mechanisms, and management strategies. RECENT FINDINGS: The recent advances in cancer immune therapy with immune checkpoint inhibitors and adoptive cell transfer have improved clinical outcomes in numerous cancers. The rising use of cancer immune therapy will lead to a higher incidence in immune-related adverse events...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28220447/current-management-of-refractory-germ-cell-tumors-and-future-directions
#3
REVIEW
J Clayton Allen, Austin Kirschner, Kristen R Scarpato, Alicia K Morgans
PURPOSE OF REVIEW: We review current management strategies for patients with relapsed and refractory germ cell tumors (GCTs), defined as relapsed or persistent disease following at least one line of cisplatin-based chemotherapy. Additionally, we discuss future directions in the management of these patients. RECENT FINDINGS: Recent studies involving targeted therapies have been disappointing. Nevertheless, studies of the management of refractory germ cell cancer are ongoing, with a focus on optimal utilization of high-dose chemotherapy and autologous stem cell transplant, as well as the role of immune checkpoint inhibitors in refractory germ cell tumors...
February 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28218707/fkbp51-immunohistochemical-expression-a-new-prognostic-biomarker-for-oscc
#4
Daniela Russo, Francesco Merolla, Massimo Mascolo, Gennaro Ilardi, Simona Romano, Silvia Varricchio, Virginia Napolitano, Angela Celetti, Loredana Postiglione, Pier Paolo Di Lorenzo, Luigi Califano, Giovanni Orabona Dell'Aversana, Fabio Astarita, Maria Fiammetta Romano, Stefania Staibano
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28214977/braf-mutated-colorectal-cancer-what-is-the-optimal-strategy-for-treatment
#5
REVIEW
Romain Cohen, Pascale Cervera, Magali Svrcek, Anna Pellat, Chantal Dreyer, Aimery de Gramont, Thierry André
The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#6
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213714/-current-biomarkers-for-gastric-cancer
#7
G B Baretton, D E Aust
Gastric cancer is still a relevant malignant disease with high morbidity and mortality. Current molecular genetic data show that gastric cancer, as other solid tumors as well, is not a single entity but consists of several molecular subtypes of gastric cancer with diverse biology. The increasing understanding of molecular pathways is the basis for innovative therapies. These either directly target altered signaling pathways or genes in tumor cells or as in immune checkpoint inhibitors, indirectly target tumor cells by blocking tumor-induced immune inhibition leading to improvement in the prognosis...
February 17, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28210995/checkpoint-inhibitors-for-the-treatment-of-renal-cell-carcinoma
#8
REVIEW
Pooja Ghatalia, Matthew Zibelman, Daniel M Geynisman, Elizabeth R Plimack
The advent of checkpoint inhibitors has revolutionized systemic therapy for many malignancies, including renal cell carcinoma (RCC) where multiple PD-1, PD-L1, and CTLA-4 inhibitors have demonstrated responses and improved survival for patients in clinical trials. Durable benefit with manageable toxicity can be achieved with these agents-but unfortunately for only a minority of individuals. Efforts are ongoing to understand mechanisms driving the response and resistance to checkpoint inhibitors in order to personalize therapy and extend benefit to more patients...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28205579/tim-3-inhibits-macrophage-control-of-listeria-monocytogenes-by-inhibiting-nrf2
#9
Zhiding Wang, Dejun Sun, Guojiang Chen, Ge Li, Shuaijie Dou, Renxi Wang, He Xiao, Chunmei Hou, Yan Li, Jiannan Feng, Beifen Shen, Gencheng Han
T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205194/novel-and-expanded-oncology-drug-approvals-of-2016-part-2-new-options-in-the-management-of-hematologic-malignancies
#10
REVIEW
Todd C Knepper, James Saller, Christine M Walko
The recent past has brought pharmacotherapeutic advances that benefit patients with hematologic malignancies. In 2016, two novel hematology drugs were approved and four previously approved hematology drugs were granted expanded use for the treatment of appropriate patient populations by the US Food and Drug Administration. These new approvals and indications represent significant steps forward in patient management: they include the first-in-class B-cell lymphoma 2 inhibitor, venetoclax, the newest targeted therapy available for the treatment of hematologic malignancies; and nivolumab, the first immune checkpoint inhibitor to be approved for treatment of a hematologic malignancy...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28205193/new-therapeutic-strategies-for-triple-negative-breast-cancer
#11
REVIEW
Borbála Székely, Andrea L M Silber, Lajos Pusztai
Relatively few clinically important therapeutic advances have occurred in the treatment of triple-negative breast cancer (TNBC) since the introduction of taxanes as adjuvant therapy over 20 years ago. However, this is rapidly changing due to a variety of conceptually important clinical trials and emerging new options such as immune checkpoint inhibitors and antibody-drug conjugates. Evidence also increasingly supports that platinum drugs and inhibitors of poly (ADP-ribose) polymerase, or PARP, are particularly effective in the treatment of germline BRCA-mutant cancers, including TNBC...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28205191/novel-and-expanded-oncology-drug-approvals-of-2016-part-1-new-options-in-solid-tumor-management
#12
REVIEW
Todd C Knepper, James Saller, Christine M Walko
The nonradiologic medical management of solid tumors has evolved from the use of traditional cytotoxic agents to modern targeted therapies, monoclonal antibodies, and immunotherapies. Advances in the understanding of cancer biology and therapeutic strategies have resulted in increasing numbers of new drug applications and approvals. Consequently, practicing oncologists need to learn how the newly available agents function and what toxicities to watch for, as well as ways to optimize the use of both new drugs and previously approved drugs with new indications...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28204866/vedolizumab-treatment-for-immune-checkpoint-inhibitor-induced-enterocolitis
#13
Viktoria Bergqvist, Erik Hertervig, Peter Gedeon, Marija Kopljar, Håkan Griph, Sara Kinhult, Ana Carneiro, Jan Marsal
Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy...
February 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#14
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#15
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28198370/smac-mimetics-synergize-with-immune-checkpoint-inhibitors-to-promote-tumour-immunity-against-glioblastoma
#16
Shawn T Beug, Caroline E Beauregard, Cristin Healy, Tarun Sanda, Martine St-Jean, Janelle Chabot, Danielle E Walker, Aditya Mohan, Nathalie Earl, Xueqing Lun, Donna L Senger, Stephen M Robbins, Peter Staeheli, Peter A Forsyth, Tommy Alain, Eric C LaCasse, Robert G Korneluk
Small-molecule inhibitor of apoptosis (IAP) antagonists, called Smac mimetic compounds (SMCs), sensitize tumours to TNF-α-induced killing while simultaneously blocking TNF-α growth-promoting activities. SMCs also regulate several immunomodulatory properties within immune cells. We report that SMCs synergize with innate immune stimulants and immune checkpoint inhibitor biologics to produce durable cures in mouse models of glioblastoma in which single agent therapy is ineffective. The complementation of activities between these classes of therapeutics is dependent on cytotoxic T-cell activity and is associated with a reduction in immunosuppressive T-cells...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28190531/cutaneous-adverse-effects-of-the-immune-checkpoint-inhibitors
#17
REVIEW
Lindsey K Collins, M Shane Chapman, Joi B Carter, Faramarz H Samie
The immune checkpoint targeted agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms...
December 14, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28188628/histopathological-aspects-of-cutaneous-erythematous-papular-eruptions-induced-by-immune-checkpoint-inhibitors-for-the-treatment-of-metastatic-melanoma
#18
Raul E Perret, Nicolas Josselin, Anne-Chantal Knol, Amir Khammari, Julie Cassecuel, Lucie Peuvrel, Brigitte Dreno
BACKGROUND: Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized. METHODS: We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists...
February 10, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#19
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28184013/phosphatidylserine-sensing-by-tam-receptors-regulates-akt-dependent-chemoresistance-and-pd-l1-expression
#20
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce D Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V Kotenko, Raymond B Birge
: Tyro3, Axl and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases (RTKs) that bind vitamin K-dependent endogenous ligands, Protein S (ProS) and Growth arrest specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radio-resistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment (TME) that can suppress host anti-tumor immunity...
February 9, 2017: Molecular Cancer Research: MCR
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