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https://www.readbyqxmd.com/read/29045513/dpyd-genotype-guided-dose-individualization-to-improve-patient-safety-of-fluoropyrimidine-therapy-call-for-a-drug-label-update
#1
L M Henricks, F L Opdam, J H Beijnen, A Cats, J H M Schellens
The fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and capecitabine, are frequently prescribed for several types of cancer, including breast, colorectal, head and neck and gastric cancer. In the current drug labels of 5-FU and capecitabine in the European Union and the United States of America no adaptive dosing strategies are incorporated for polymorphic metabolism of 5-FU.Although treatment with fluoropyrimidines is generally well tolerated, a major clinical limitation is that a proportion of the treated population experiences severe, sometimes life-threatening, fluoropyrimidine-related toxicity...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29031066/serendipitous-discovery-of-potent-human-head-and-neck-squamous-cell-carcinoma-anti-cancer-molecules-a-fortunate-failure-of-a-rational-molecular-design
#2
Chiara Zagni, Venerando Pistarà, Luciana A Oliveira, Rogerio M Castilho, Giovanni Romeo, Ugo Chiacchio, Antonio Rescifina
Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity...
October 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#3
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28910901/-clinical-research-on-immune-checkpoint-and-head-and-neck-squamous-cell-carcinoma
#4
D Yu, X M Qi, X Zhao, Y Liu, K Xue, C S Jin, L J Wen
T cell immune checkpoint pathways contribute to tumor immune escape. Many studies have shown that immune checkpoint is demonstrably correlated with tumor grade or prognosis in several types of malignancies and immune checkpoint has become a new biological index for tumor detection and prognosis. Immune checkpoint inhibitors have shown promising tumor outcomes in clinical trials for some advanced solid tumors and it will become a new target for cancer immunotherapy. In this review we will explore the correlation between expressions of immune checkpoint-associated genes and proteins in immune microenviroment and prognosis of head and neck squamous cell carcinoma, and specifically will discuss how this pathway can be manipulated with immune therapeutic drugs...
September 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28910149/dual-targeting-of-epidermal-growth-factor-receptor-and-her3-by-mehd7945a-as-monotherapy-or-in-combination-with-cisplatin-partially-overcomes-cetuximab-resistance-in-head-and-neck-squamous-cell-carcinoma-cell-lines
#5
Ines De Pauw, An Wouters, Jolien Van den Bossche, Vanessa Deschoolmeester, Hasan Baysal, Patrick Pauwels, Marc Peeters, Jan B Vermorken, Filip Lardon
Aberrant signaling of the epidermal growth factor receptor (EGFR) plays a crucial role in the tumorigenesis of many cancer types, including head and neck squamous cell carcinoma (HNSCC), making it a compelling drug target. After initial promising results of EGFR-targeted therapies such as cetuximab, the problem of therapeutic resistance is emerging and new treatment options are necessary. In contrast to first-generation EGFR inhibitors, MEHD7945A (duligotuzumab) is a monoclonal antibody with dual EGFR/HER3 specificity...
September 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28901268/nrg1-erbb-lost-in-translation-a-new-paradigm-for-lung-cancer
#6
Domenico Trombetta, Antonio Rossi, Federico Pio Fabrizio, A Sparaneo, Paolo Graziano, Vito Michele Fazio, Lucia Anna Muscarella
The ErbB network of receptor tyrosine kinases represents one of the best examples of how the understanding of molecular basis of tumor pathogenesis can give a significant improvement for patients treatment, suggesting new therapeutic options to overcome acquired treatment resistance. This amazing bridge between growth factor receptors and cancer has been consolidated during the last decades through the identification of many driver mutations in the gene key of the RTKs network. Unexpected molecular lesions of the NRG1 gene followed by an aberrant ErbB signaling were recently described as a new molecular features of non-small cell lung cancer, but it has been also sporadically reported in other tumors...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#7
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28881692/cabazitaxel-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-phase-ii-unicancer-trial-orl03
#8
Jerome Fayette, Joel Guigay, Christophe Le Tourneau, Marian Degardin, Frederic Peyrade, Eve-Marie Neidhardt, Marie-Paule Sablin, Caroline Even, Florence Orlandini, Béata Juzyna, Carine Bellera
Treatments are limited after platinum Cetuximab or anti-PD1 failure for patients with recurrent/metastatic head and neck squamous cell carcinoma. Cabazitaxel has increased overall survival in hormone-refractory metastatic prostate cancer after failure of Docetaxel. Our aim was to detect a signal of activity with Cabazitaxel in patients with head and neck cancer who had failed platinum-, Cetuximab- and taxanes-based chemotherapy. This multicenter phase II trial included progressive patients with an ECOG ≤2...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28873083/sklb188-inhibits-the-growth-of-head-and-neck-squamous-cell-carcinoma-by-suppressing-egfr-signalling
#9
Mansoureh Barzegar, Shuang Ma, Chao Zhang, Xin Chen, Ying Gu, Chaowei Shang, Xiaojuan Jiang, Jiao Yang, Cherie-Ann Nathan, Shengyong Yang, Shile Huang
BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) occurs in approximately 90% of head and neck squamous cell carcinoma (HNSCC), and is correlated with poor prognosis. Thus, targeting EGFR is a promising strategy for treatment of HNSCC. Several small molecule EGFR inhibitors have been tested in clinical trials for treatment of HNSCC, but none of them are more effective than the current chemotherapeutic drugs. Thus, it is urgently needed to develop novel EGFR inhibitors for HNSCC treatment...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28837080/activation-of-matrix-hyaluronan-mediated-cd44-signaling-epigenetic-regulation-and-chemoresistance-in-head-and-neck-cancer-stem-cells
#10
REVIEW
Lilly Y W Bourguignon, Christine Earle, Marisa Shiina
Head and neck squamous cell carcinoma (HNSCC) is a solid tumor composed by a genotypically and phenotypically heterogeneous population of neoplastic cells types. High recurrence rate and regional metastases lead to major morbidity and mortality. Recently, many studies have focused on cellular and molecular mechanisms of tumor progression that can help to predict prognosis and to choose the best therapeutic approach for HNSCC patients. Hyaluronan (HA), an important glycosaminoglycan component of the extracellular matrix (ECM), and its major cell surface receptor, CD44, have been suggested to be important cellular mediators influencing tumor progression and treatment resistance in head and neck cancer...
August 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#11
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28791405/silibinin-suppresses-bladder-cancer-cell-malignancy-and-chemoresistance-in-an-nf-%C3%AE%C2%BAb-signal-dependent-and-signal-independent-manner
#12
Yi Sun, Zhenfeng Guan, Wencai Zhao, Yazhuo Jiang, Qing Li, Yongyi Cheng, Yonggang Xu
Because bladder cancer (BCa) is the 9th most common malignant tumor and 13th leading cause of death due to cancer, therapeutic approaches have attracted a great deal of attention from both clinicians and BCa patients. Although the development of surgery and targeted drugs has brought new challenges for the traditional concept of BCa therapy, various types of chemotherapy remain the final treatment method for many BCa patients. However, chemoresistance inevitably appears, leading to the failure of chemotherapy...
August 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28761758/the-european-society-for-medical-oncology-magnitude-of-clinical-benefit-scale-field-tested-in-infrequent-tumour-entities-an-extended-analysis-of-its-feasibility-at-the-medical-university-of-vienna
#13
Barbara Kiesewetter, Markus Raderer, Gerald W Prager, Thorsten Fuereder, Christine Marosi, Matthias Preusser, Michael Krainer, Gottfried J Locker, Thomas Brodowicz, Christoph C Zielinski
BACKGROUND: The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a new tool to quantify the clinical benefit that may be anticipated from a novel anticancer treatment. We present here an analysis on the feasibility of the ESMO-MCBS in less frequent tumour entities. METHODS: This study evaluates the practicability of the ESMO-MCBS for metastatic neuroendocrine tumours (NETs), soft tissue sarcomas, glioblastoma, thyroid cancer, pancreatic cancer, head/neck cancer, urothelial cancer and ovarian cancer at the Medical University Vienna...
2017: ESMO Open
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#14
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28719033/identification-of-driver-copy-number-alterations-in-diverse-cancer-types-and-application-in-drug-repositioning
#15
Wenbin Zhou, Zhangxiang Zhao, Ruiping Wang, Yue Han, Chengyu Wang, Fan Yang, Ya Han, Haihai Liang, Lishuang Qi, Chenguang Wang, Zheng Guo, Yunyan Gu
Results from numerous studies suggest an important role for somatic copy number alterations (SCNAs) in cancer progression. Our work aimed to identify the drivers (oncogenes or tumor suppressor genes) that reside in recurrently aberrant genomic regions, including a large number of genes or non-coding genes, which remain a challenge for decoding the SCNAs involved in carcinogenesis. Here, we propose a new approach to comprehensively identify drivers, using 8740 cancer samples involving 18 cancer types from The Cancer Genome Atlas (TCGA)...
October 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28714398/nutlin-3-a-p53-mdm2-antagonist-for-nasopharyngeal-carcinoma-treatment
#16
Voon Yee-Lin, Wong Pooi-Fong, Alan Khoo Soo-Beng
Nasopharyngeal carcinoma (NPC) is a form of head and neck cancer of multifactorial etiologies that is highly prevalent among men in the populations of Southern China and Southeast Asia. NPC has claimed many thousands of lives worldwide; but the low awareness of NPC remains a hindrance in early diagnosis and prevention of the disease. NPC is highly responsive to radiotherapy and chemotherapy, but radiocurable NPC is still dependent on concurrent treatment of megavoltage radiotherapy with chemotherapy. Despite a significant reduction in loco-regional and distant metastases, radiotherapy alone has failed to provide a significant improvement in the overall survival rate of NPC, compared to chemotherapy...
July 17, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28671620/epithelial-to-mesenchymal-transition-in-the-pathogenesis-and-therapy-of-head-and-neck-cancer
#17
REVIEW
Julia Thierauf, Johannes Adrian Veit, Jochen Hess
Head and neck cancer (HNC) is one of the most prevalent human malignancies worldwide, with a high morbidity and mortality. Implementation of interdisciplinary treatment modalities has improved the quality of life, but only minor changes in overall survival have been achieved over the past decades. Main causes for treatment failure are an aggressive and invasive tumor growth in combination with a high degree of intrinsic or acquired treatment resistance. A subset of tumor cells gain these properties during malignant progression by reactivating a complex program of epithelia-to-mesenchymal transition (EMT), which is integral in embryonic development, wound healing, and stem cell behavior...
July 3, 2017: Cancers
https://www.readbyqxmd.com/read/28571578/immunotherapy-in-head-and-neck-cancer-aiming-at-extreme-precision
#18
Petr Szturz, Jan B Vermorken
BACKGROUND: Locoregionally advanced, recurrent, and metastatic squamous cell carcinomas of the head and neck (SCCHN) remain difficult to treat disease entities, in which systemic treatment often forms an integral part of their management. Immunotherapy is based on functional restoration of the host immune system, helping to counteract various tumour evasion strategies. Broadly, immunotherapeutic approaches encompass tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating agents...
June 2, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28550447/trends-in-surgical-research-in-head-and-neck-cancer
#19
REVIEW
Genrich Tolstonog, Christian Simon
The task of surgical research is to improve the efficacy of available surgical therapeutic modalities, develop new ones, and balance this well with favorable functional outcome. Therefore, surgical research is composed of a translational and a clinical component. In translational surgical research, animal models are used to better understand the biology of head and neck cancers, but even more importantly, the biology of changes to the disease and the microenvironment created by surgical interventions. Animal models additionally allow for the development of image-guided surgery systems, novel strategies of intraoperative adjuvant treatment, and patient "avatars" to test innovative anticancer drug combinations...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28496478/study-of-crocin-radiotherapy-induced-cytotoxicity-and-apoptosis-in-the-head-and-neck-cancer-hn-5-cell-line
#20
Vahid Vazifedan, Seyed Hadi Mousavi, Javad Sargolzaei, Shokouhozaman Soleymanifard, Azar Fani Pakdel
Malignant tumors of head and neck carcinomas are the sixth most common type of cancer. Current systemic therapies for cancer show side effects in normal tissues and short-term efficacy due to drug resistance. Consequently, there is much interest in identifying new drugs for cancer treatment. Crocin (an active ingredient of saffron) has been shown to have cytotoxic effects on cancer cell lines. Chemo radiotherapy is the standard treatment for head and neck cancer. In the present study, the cytotoxic effects, inducing apoptosis and the radiation sensitivity of crocin were evaluated in the head and neck cancer cell line (HN-5)...
2017: Iranian Journal of Pharmaceutical Research: IJPR
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