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New drugs head neck cancer

Younghyoun Yoon, Aaron M Mohs, Michael C Mancini, Shuming Nie, Hyunsuk Shim
Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%-30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery...
September 2016: Tomography: a Journal for Imaging Research
Santosh Lakshmi Gande, Krishna Saxena, Sridhar Sreeramulu, Verena Linhard, Denis Kudlinzki, Stephanie Heinzlmeir, Andreas J Reichert, Arne Skerra, Bernhard Kuster, Harald Schwalbe
The receptor tyrosine kinase EPHA2 is overexpressed in several cancer entities (breast, head and neck, non-small cell lung cancer). Small molecule-based inhibition of the activity of the EPHA2 kinase domain (KD) has been seen as an important strategy for achieving therapeutic intervention. However, obtaining structural information by protein crystallography or by NMR spectroscopy aiding drug discovery, has been severely hampered due to the lack of pure and homogeneous protein. Here different fragments of the EPHA2 KD were expressed and purified from both bacterial (Escherichia coli BL21 (DE3) cells) and insect cells (Spodoptera frugiperda, Sf9 cells)...
September 29, 2016: Chembiochem: a European Journal of Chemical Biology
Stefan Hartmann, Jennifer R Grandis
INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and the majority of patients present with advanced stage disease. Chemotherapy is an important component of head and neck cancer treatment regimens and has shown beneficial effects in locally advanced and recurrent/metastatic stages of disease. Approximately 25% of HNSCC patients are aged 70 and older, often associated with co-morbid medical conditions. Most clinical trials exclude patients of advanced chronological age such that valid information about the efficacy and safety of drugs and treatment regimens in elderly patients is not available...
October 2016: Expert Opinion on Pharmacotherapy
Petr Szturz, Jan B Vermorken
The demographics of squamous cell carcinoma of the head and neck (SCCHN) is marked by a growing number of patients aged 65 and over, which is in line with global projections for other cancer types. In developed countries, more than half of new SCCHN cases are diagnosed in older people, and in 15 years from now, the proportion is expected to rise by more than 10%. Still, a high-level evidence-based consensus to guide the clinical decision process is strikingly lacking. The available data from retrospective studies and subset analyses of prospective trials suffer from a considerable underrepresentation of senior participants...
2016: Frontiers in Oncology
Vincent Sibaud, Nicole R Lebœuf, Henri Roche, Viswanath R Belum, Laurence Gladieff, Marion Deslandres, Marion Montastruc, Audrey Eche, Emmanuelle Vigarios, Florence Dalenc, Mario E Lacouture
Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents...
August 22, 2016: European Journal of Dermatology: EJD
Hongquan Li, Linjun Shi, Jie Wei, Chenping Zhang, Zengtong Zhou, Lan Wu, Wei Liu
Salvianolic acid B (SalB) was demonstrated to be a promising chemopreventive agent for head and neck squamous cell carcinoma (HNSCC) in the previous studies by our and other research institution, but the properties like low efficacy, poor systemic delivery, and low bioavailability has hampered its clinical applications. To continue our research program focused on the use of natural compounds on cancer chemoprevention, we propose a first example of phospholipid complex loaded nanoparticles (PLC-NPs) encapsulating SalB as a potential carrier for intervention of HNSCC (HN13, HN30) cells and precancer Leuk1 cells in this study...
November 1, 2016: Colloids and Surfaces. B, Biointerfaces
Hiroshi Fukuhara, Yasushi Ino, Tomoki Todo
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe...
August 3, 2016: Cancer Science
Antonio Cortese, Giuseppe Pantaleo, Massimo Amato, Logan Lawrence, Veronica Mayes, Linda Brown, Maria Rosaria Sarno, Jagan Valluri, Pier Paolo Claudio
INTRODUCTION: Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem cells (CSCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy drug response assay (ChemoID(®)), which measures the sensitivity of CSCs as well as the bulk of tumor cells to a variety of chemotherapy agents to assist an oncologist in making treatment decisions...
2016: International Journal of Surgery Case Reports
Miguel Angel Pavón, Irene Arroyo-Solera, Maria Virtudes Céspedes, Isolda Casanova, Xavier León, Ramón Mangues
There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition...
June 30, 2016: Oncotarget
Shih-Wei Yang, Chi-Ying Tsai, Yi-Chun Pan, Chun-Nan Yeh, Jong-Hwei S Pang, Masashi Takano, Atsushi Kittaka, Horng-Heng Juang, Tai C Chen, Kun-Chun Chiang
Even with multidisciplinary treatment, the prognosis and quality of life of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are still not satisfactory. Previously, 19-Nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 (MART-10), the new brand 1α,25(OH)2D3 analog, has been demonstrated to be an effective drug to inhibit HNSCC growth in vitro. Since most cancer patients die of metastasis, in this study, the antimetastatic effect of MART-10 on HNSCC was investigated. Our results reveal that both 1α,25(OH)2D3 and MART-10 effectively repressed the migration and invasion of HNSCC cells, with MART-10 being much more potent than 1α,25(OH)2D3...
2016: Drug Design, Development and Therapy
C Granier, S Karaki, H Roussel, C Badoual, T Tran, M Anson, E Fabre, S Oudard, E Tartour
Cancer immunotherapy has occupied a marginal therapeutic option in cancer despite strong arguments documenting the role of the immune system in controlling the proliferation of cancers. The recent success of immunotherapy results from a change in the past paradigm. From now on, the goal is not only to activate the immune system against tumor, but also to take account of the immunosuppressive tumor microenvironment Among these mechanisms, negative costimulatory molecules (CTLA-4, PD-1, etc.) expressed by T cells in the tumor could explain their lack of effectiveness in inhibiting tumor growth...
June 28, 2016: La Revue de Médecine Interne
Sandra Schmitz, Jean-Pascal Machiels
The survival rate for patients with advanced stages of squamous cell carcinoma of the head and neck (SCCHN) remains poor despite multimodal treatment options. Cetuximab, an anti-EGFR inhibitor, is the only FDA-approved targeted agent for this disease. Recent findings have implicated modifications of the microenvironment and, consequently, phenotypical modifications of the cancer cell, in treatment resistance mechanisms. For many years, cancer research has focused mainly on targetable sites on or inside the cancer cell...
July 2016: Current Treatment Options in Oncology
M E Gray, S Lee, A L McDowell, M Erskine, Q T M Loh, O Grice, D J Argyle, G T Bergkvist
Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro...
May 27, 2016: Veterinary and Comparative Oncology
Sean Henry, Ria Kidner, Mary R Reisenauer, Igor V Magedov, Robert Kiss, Véronique Mathieu, Florence Lefranc, Ramesh Dasari, Antonio Evidente, Xiaojie Yu, Xiuye Ma, Alexander Pertsemlidis, Regina Cencic, Jerry Pelletier, David A Cavazos, Andrew J Brenner, Alexander V Aksenov, Snezna Rogelj, Alexander Kornienko, Liliya V Frolova
Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others...
September 14, 2016: European Journal of Medicinal Chemistry
Anushree Tripathi, Krishna Misra
P-glycoprotein (P-gp) is well known to cause multidrug resistance (MDR) in cancer cells. This MDR leads to cancer recurrence which is a major obstacle in cancer treatment. High P-gp expression has been observed in the population of cancer stem cells (CSCs) having self-renewal potential. Early detection and inhibition of these CSCs is directly beneficial to cancer treatment. In this study coumarin derivatives are used to inhibit efflux process and thereby enhance bioavailability of various drugs like paclitaxel (PTX)...
2016: Combinatorial Chemistry & High Throughput Screening
Munindra Ruwali, Ankur Dhawan, Mohan C Pant, Qamar Rahman, S M Paul Khurana, Devendra Parmar
Head and neck squamous cell carcinoma (HNSCC) describes a wide range of malignant tumors which originate in the upper aerodigestive tract and have a multifactorial origin involving both genetic and lifestyle risk factors. The clinical management of head and neck cancer involves surgery, radiotherapy, and chemotherapy. With the advances in treatment strategies for HNSCC, newer targeted therapies are adding to the progress already achieved in the multimodality management of patients although the problems of differences in drug response and adverse drug reactions are still grave concerns...
2016: Oncology Research and Treatment
Daška Štulhofer Buzina, Ivana Martinac, Daniela Ledić Drvar, Romana Čeović, Ivan Bilić, Branka Marinović
Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2)...
April 2016: Acta Dermatovenerologica Croatica: ADC
Carmine Pinto, Carlo A Barone, Giampiero Girolomoni, Elvio G Russi, Marco C Merlano, Daris Ferrari, Evaristo Maiello
OBJECTIVES: Cetuximab was shown in phase III clinical trials to improve chemotherapy efficacy in patients with advanced colorectal and head-neck cancer. Appropriate management of skin reactions associated with epidermal growth factor receptor inhibitor therapy is necessary to allow adequate drug compliance and to improve patient quality of life and outcomes. METHODS: The RAND/UCLA Appropriateness Method was used by a group of experts to produce new Italian recommendations on the management of skin reactions in this setting...
August 2016: American Journal of Clinical Oncology
Paolo Bossi, Salvatore Alfieri
INTRODUCTION: In the treatment of advanced/metastatic head and neck cancer (HNC), resistance to chemotherapy and to anti-EGFR agents remains a major issue, and new molecular drugs are eagerly awaited. Over the last decade, knowledge of the genetic landscape of HNC has rapidly grown. However, no tailored therapeutic intervention targeting HNC molecular abnormalities is currently available outside from clinical trials. AREAS COVERED: In this review, the authors analyze new drugs in the HNC setting which have been investigated in recently published trials or are currently being investigated...
July 2016: Expert Opinion on Investigational Drugs
Pia M Challita-Eid, Daulet Satpayev, Peng Yang, Zili An, Karen Morrison, Yuriy Shostak, Arthur Raitano, Rossana Nadell, Wendy Liu, Dawn Ratay Lortie, Linnette Capo, Alla Verlinsky, Monica Leavitt, Faisal Malik, Hector Aviña, Claudia I Guevara, Nick Dinh, Sher Karki, Banmeet S Anand, Daniel S Pereira, Ingrid B J Joseph, Fernando Doñate, Kendall Morrison, David R Stover
The identification of optimal target antigens on tumor cells is central to the advancement of new antibody-based cancer therapies. We performed suppression subtractive hybridization and identified nectin-4 (PVRL4), a type I transmembrane protein and member of a family of related immunoglobulin-like adhesion molecules, as a potential target in epithelial cancers. We conducted immunohistochemical analysis of 2,394 patient specimens from bladder, breast, lung, pancreatic, ovarian, head/neck, and esophageal tumors and found that 69% of all specimens stained positive for nectin-4...
May 15, 2016: Cancer Research
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