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https://www.readbyqxmd.com/read/29158469/molecular-basis-for-necitumumab-inhibition-of-egfr-variants-associated-with-acquired-cetuximab-resistance
#1
Atrish Bagchi, Jaafar N Haidar, Scott W Eastman, Michal Vieth, Michael Topper, Michelle D Iacolina, Jason M Walker, Amelie Forest, Yang Shen, Ruslan D Novosiadly, Kathryn M Ferguson
Acquired resistance to cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR), impacts clinical benefit in head and neck, and colorectal cancers (CRC). One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab resistance substitution, S468R (or S492R, depending on the amino acid numbering system)...
November 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29156447/pd-1-blockade-in-advanced-nsclc-a-focus-on-pembrolizumab
#2
REVIEW
Solange Peters, Keith M Kerr, Rolf Stahel
Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts...
October 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29131763/immune-checkpoint-inhibitor-cancer-therapy-spectrum-of-imaging-findings
#3
Gary X Wang, Vikram Kurra, Justin F Gainor, Ryan J Sullivan, Keith T Flaherty, Susanna I Lee, Florian J Fintelmann
Immune checkpoint inhibitors are a new class of cancer therapeutics that have demonstrated striking successes in a rapid series of clinical trials. Consequently, these drugs have dramatically increased in clinical use since being first approved for advanced melanoma in 2011. Current indications in addition to melanoma are non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, and classical Hodgkin lymphoma. A small subset of patients treated with immune checkpoint inhibitors undergoes an atypical treatment response pattern termed pseudoprogression: New or enlarging lesions appear after initiation of therapy, thereby mimicking tumor progression, followed by an eventual decrease in total tumor burden...
November 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29124000/human-papillomavirus-associated-head-and-neck-squamous-cell-carcinoma-controversies-and-new-concepts
#4
REVIEW
Nuzhat Husain, Azfar Neyaz
High-risk human papillomavirus (HR-HPV) is a causative agent for an increasing subset of oropharyngeal squamous cell carcinoma. HPV 16 accounts for 90% of cases. The chance for malignant transformation due to infection with high-risk HPV is proportional to the expression of the viral oncogene products E6 and E7, which inactivate p53 and retinoblastoma (Rb) tumor suppressor functions. P16 is a surrogate marker of HPV associated HNSCC and 2+/3+ expression in more than 75% cells is diagnostic. Molecular demonstration of integrated virus by in situ hybridization is specific but has low sensitivity...
September 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/29097914/cd44v6-targeted-imaging-of-head-and-neck-squamous-cell-carcinoma-antibody-based-approaches
#5
REVIEW
Diana Spiegelberg, Johan Nilvebrant
Head and neck squamous cell carcinoma (HNSCC) is a common and severe cancer with low survival rate in advanced stages. Noninvasive imaging of prognostic and therapeutic biomarkers could provide valuable information for planning and monitoring of the different therapy options. Thus, there is a major interest in development of new tracers towards cancer-specific molecular targets to improve diagnostic imaging and treatment. CD44v6, an oncogenic variant of the cell surface molecule CD44, is a promising molecular target since it exhibits a unique expression pattern in HNSCC and is associated with drug- and radio-resistance...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29082766/new-developments-and-clinical-transition-of-hyaluronic-acid-based-nanotherapeutics-for-treatment-of-cancer-reversing-multidrug-resistance-tumour-specific-targetability-and-improved-anticancer-efficacy
#6
Muhammad Hassan Safdar, Zahid Hussain, Mohammed A S Abourehab, Humna Hasan, Sajal Afzal, Hnin Ei Thu
This review aims to overview and critically analyses recent developments in achieving tumour-specific delivery of anticancer agents, maximizing anticancer efficacy, and mitigating tumour progression and off-target effects. Stemming from critical needs to develop target-specific delivery vehicles in cancer therapy, various hyaluronic acid (HA)-conjugated nanomedicines have been fabricated owing to their biocompatibility, safety, tumour-specific targetability of drugs and genes, and proficient interaction with cluster-determinant-44 (CD44) receptors over-expressed on the surface of tumour cells...
October 30, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29069723/repurposing-albendazole-new-potential-as-a-chemotherapeutic-agent-with-preferential-activity-against-hpv-negative-head-and-neck-squamous-cell-cancer
#7
Farhad Ghasemi, Morgan Black, Frederick Vizeacoumar, Nicole Pinto, Kara M Ruicci, Carson Cao Son Huu Le, Matthew R Lowerison, Hon Sing Leong, John Yoo, Kevin Fung, Danielle MacNeil, David A Palma, Eric Winquist, Joe S Mymryk, Paul C Boutros, Alessandro Datti, John W Barrett, Anthony C Nichols
Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045513/dpyd-genotype-guided-dose-individualization-to-improve-patient-safety-of-fluoropyrimidine-therapy-call-for-a-drug-label-update
#8
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
#9
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...
December 1, 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
September 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
#19
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
#20
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
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