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https://www.readbyqxmd.com/read/29595111/looking-for-new-inhibitors-for-the-epidermial-growth-factor-receptor
#1
Riccardo Concu, Maria Natalia DiasSoeiro Cordeiro
Epidermial growth factor receptor (EGFR) is still the main target of the head and neck squamous cell cancer (HNSCC) because its overexpression has been detected in more than 90% of this type of cancer. This overexpression is usually linked with more aggressive disease, increased resistance to chemotherapy and radiotherapy, increased metastasis, inhibition of apoptosis, promotion of neoplastic angiogenesis, and, finally, poor prognosis and decreased survival. Due to this, is the main target in the search of new drugs and inhibitors candidates able to downturn this overexpression...
March 29, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29552307/characterization-of-7a7-an-anti-mouse-egfr-monoclonal-antibody-proposed-to-be-the-mouse-equivalent-of-cetuximab
#2
Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29547766/immunotherapy-in-head-and-neck-cancers-a-new-challenge-for-immunologists-pathologists-and-clinicians
#3
REVIEW
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
March 1, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29516950/mechanisms-correlated-with-chemotherapy-resistance-in-tongue-cancers
#4
REVIEW
Guanghong Han, Chengbi Xu, Dan Yu
Tongue cancer is one of the most common and deadly types of head and neck cancer. The incidence of tongue cancer has been particularly high and remained been increasing in some countries. A main reason for poor prognosis and clinical outcome for tongue cancer was its resistance to chemotherapies, behind which the mechanisms have been not clear. In this review, we summarized literatures published in recent years and listed the proteins, biomacromolecules, and signaling pathways related to this drug resistance...
January 2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29497306/new-developments-in-the-management-of-head-and-neck-cancer-impact-of-pembrolizumab
#5
REVIEW
Khalil Saleh, Roland Eid, Fady Gh Haddad, Nadine Khalife-Saleh, Hampig Raphaël Kourie
Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29474961/the-presence-of-glutamate-residues-on-the-pas-sequence-of-the-stimuli-sensitive-nano-ferritin-improves-in-vivo-biodistribution-and-mitoxantrone-encapsulation-homogeneity
#6
Elisabetta Falvo, Francesca Malagrinò, Alessandro Arcovito, Francesco Fazi, Gianni Colotti, Elisa Tremante, Patrizio Di Micco, Aldo Braca, Roberta Opri, Alessandro Giuffrè, Giulio Fracasso, Pierpaolo Ceci
A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29474420/a-new-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-the-determination-of-paclitaxel-and-6%C3%AE-hydroxy-paclitaxel-in-human-plasma-development-validation-and-application-in-a-clinical-pharmacokinetic-study
#7
Bianca Posocco, Mauro Buzzo, Andrea Follegot, Luciana Giodini, Roberto Sorio, Elena Marangon, Giuseppe Toffoli
Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found...
2018: PloS One
https://www.readbyqxmd.com/read/29454236/stingel-controlled-release-of-a-cyclic-dinucleotide-for-enhanced-cancer-immunotherapy
#8
David G Leach, Neeraja Dharmaraj, Stacey L Piotrowski, Tania L Lopez-Silva, Yu L Lei, Andrew G Sikora, Simon Young, Jeffrey D Hartgerink
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call "STINGel...
February 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#9
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
April 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29420101/leveraging-genomics-for-head-and-neck-cancer-treatment
#10
J D Kemmer, D E Johnson, J R Grandis
The genomic landscape of head and neck squamous cell carcinoma (HNSCC) has been recently elucidated. Key epigenetic and genetic characteristics of this cancer have been reported and substantiated in multiple data sets, including those distinctive to the growing subset of human papilloma virus (HPV)-associated tumors. This increased understanding of the molecular underpinnings of HNSCC has not resulted in new approaches to treatment. Three Food and Drug Administration-approved molecular targeting agents are currently available to treat recurrent/metastatic disease, but these have exhibited efficacy only in subsets of HNSCC patients, and thus surgery, chemotherapy, and/or radiation remain as standard approaches...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29374693/association-of-eif4e-and-sparc-expression-with-lymphangiogenesis-and-lymph-node-metastasis-in-hypopharyngeal-cancer
#11
Benjamin Philipp Ernst, Caja Mikstas, Timo Stöver, Roland Stauber, Sebastian Strieth
BACKGROUND/AIM: Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets. MATERIALS AND METHODS: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29345579/genistein-as-a-potential-anticancer-agent-against-head-and-neck-squamous-cell-carcinoma
#12
Fatima Ardito, Giovanni Di Gioia, Mario Roberto Pellegrino, Lorenzo Lo Muzio
The use of nutraceuticals as protection drugs against chronic diseases gained a vast success. Many studies found that nutraceuticals may reduce the tumorigenic actions of carcinogens, inhibiting the adhesion and proliferation of tumor cells. Genistein is a natural isoflavone preventing osteoporosis, menopause problems and heart diseases. It is also known in China and Japan for its anticancer properties. The available treatment protocols for Head and neck squamous cell cancer (HNSCC) have led to poor results and new therapies are necessary...
January 16, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29334764/development-of-gene-therapeutics-for-head-and-neck-cancer-in-china-from-bench-to-bedside
#13
Wei Guo, Hao Song
Head and neck cancer represents the seventh most common cancer worldwide. Although multidisciplinary sequential treatments have been used, there is still an urgent need for new treatment approaches that can effectively improve the outcomes of patients with advanced stages of head and neck cancer. Gene therapy is a rapidly evolving field in cancer therapy that has been shown to improve the efficacy of antitumor treatment. China is at the forefront in clinical trials and practice of gene therapy. Chinese researchers have mainly focused on gene therapeutics based on oncolytic virus and recombinant adenovirus expressing p53, antiangiogenesis factor or herpes simplex virus-thymidine kinase...
February 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29332581/cetuximab-and-the-head-and-neck-squamous-cell-cancer
#14
Riccardo Concu, Maria Natalia Dias Soeiro Cordeiro
The head and neck squamous cell cancer (HNSCC) is the most common type of head and neck cancer (more than 90%), and all over the world more than a half million people have been developing this cancer in the last years. This type of cancer is usually marked by a poor prognosis with a really significant morbidity and mortality. Cetuximab received early favor as an exciting and promising new therapy with relatively mild side effect, and due to this received authorization in the 2004 from the European Medicines Agency (EMA) and in the 2006 from the Food and Drug Association (FDA) for the treatment of patients with squamous cell cancer of the head and neck in combination with radiation therapy for locally advanced disease...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332580/aurora-kinase-inhibitors-in-head-and-neck-cancer
#15
Guangying Qi, Jing Liu, Sisi Mi, Takaaki Tsunematsu, Shengjian Jin, Wenhua Shao, Tian Liu, Naozumi Ishimaru, Bo Tang, Yasusei Kudo
Aurora kinases are a group of serine/threonine kinases responsible for the regulation of mitosis. In recent years, with the increase in Aurora kinase-related research, the important role of Aurora kinases in tumorigenesis has been gradually recognized. Aurora kinases have been regarded as a new target for cancer therapy, resulting in the development of Aurora kinase inhibitors. The study and application of these small-molecule inhibitors, especially in combination with chemotherapy drugs, represents a new direction in cancer treatment...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29306329/gene-expression-signature-regulated-by-the-keap1-nrf2-cul3-axis-is-associated-with-a-poor-prognosis-in-head-and-neck-squamous-cell-cancer
#16
Akhileshwar Namani, Md Matiur Rahaman, Ming Chen, Xiuwen Tang
BACKGROUND: NRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers...
January 6, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29295635/real-world-utilization-of-molecular-diagnostic-testing-and-matched-drug-therapies-in-the-treatment-of-metastatic-cancers
#17
Anita Chawla, Miranda Peeples, Nanxin Li, Rachel Anhorn, Jason Ryan, James Signorovitch
AIMS: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. METHODS: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability...
January 19, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29284308/fighting-cancer-with-viruses-oncolytic-virus-therapy-in-china
#18
Ding Wei, Jing Xu, Xin-Yuan Liu, Zhi-Nan Chen, Huijie Bian
As part of oncolytic virotherapy to treat cancer, oncolytic viruses (OVs) can selectively infect tumor cells to promote oncolysis of cancer cells, local immunological reactions, and systemic antitumor immunity with minimal toxicity to normal tissues. The immunostimulatory properties of OVs provide enormous benefits for the treatment of cancer. A variety of OVs, including genetically engineered and natural viruses, have shown promise in preclinical models and clinical studies. In 2005, the China Food and Drug Administration approved its first OV drug, Oncorine (H101), for treatment of advanced head and neck cancer...
February 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29158469/molecular-basis-for-necitumumab-inhibition-of-egfr-variants-associated-with-acquired-cetuximab-resistance
#19
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 EGFR, impacts clinical benefit in head and neck, and colorectal cancers. 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-resistant substitution, S468R (or S492R, depending on the amino acid numbering system). We determined an X-ray crystal structure to 2...
February 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29156447/pd-1-blockade-in-advanced-nsclc-a-focus-on-pembrolizumab
#20
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...
January 2018: Cancer Treatment Reviews
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