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https://www.readbyqxmd.com/read/28337370/role-of-epidermal-growth-factor-receptor-in-lung-cancer-and-targeted-therapies
#1
REVIEW
Tie-Cheng Liu, Xin Jin, Yan Wang, Ke Wang
Lung cancer is the foremost cause of cancer-related deaths world-wide. Both, the major forms of lung cancer, Non-small cell lung cancer (NSCLC) and Small cell lung cancers (SCLC), have responded effectively to chemo-, radiation and adjuvant-therapies. Tumor removal through surgery also appeared as a good therapeutic strategy. However, these therapies demonstrated unfavourable side-effects, and hence novel drugs targeting lung cancer emerged essential. Activation of epidermal growth factor receptor (EGFR)-tyrosine kinases is a key reason for lung cancer progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28328812/overall-survival-of-patients-with-kras-wild-type-tumor-treated-with-folfox-forfiri%C3%A2-cetuximab-as-the-first-line-treatment-for-metastatic-colorectal-cancer-a-meta-analysis
#2
Ya-Fan Yang, Gui-Ying Wang, Jing-Li He, Feng-Peng Wu, Yan-Ni Zhang
The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ± cetuximab was compared...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328302/pembrolizumab-for-platinum-and-cetuximab-refractory-head-and-neck-cancer-results-from-a-single-arm-phase-ii-study
#3
Joshua Bauml, Tanguy Y Seiwert, David G Pfister, Francis Worden, Stephen V Liu, Jill Gilbert, Nabil F Saba, Jared Weiss, Lori Wirth, Ammar Sukari, Hyunseok Kang, Michael K Gibson, Erminia Massarelli, Steven Powell, Amy Meister, Xinxin Shu, Jonathan D Cheng, Robert Haddad
Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks...
March 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28327895/cetuximab-rechallenge-in-metastatic-colorectal-cancer-patients-how-to-come-away-from-acquired-resistance
#4
D Santini, B Vincenzi, R Addeo, C Garufi, G Masi, M Scartozzi, A Mancuso, A M Frezza, O Venditti, M Imperatori, G Schiavon, G Bronte, G Cicero, F Recine, E Maiello, S Cascinu, A Russo, A Falcone, G Tonini
No abstract text is available yet for this article.
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325631/new-concepts-of-personalized-therapy-in-salivary-gland-carcinomas
#5
REVIEW
Gunter Keller, Diana Steinmann, Alexander Quaas, Viktor Grünwald, Stefan Janssen, Kais Hussein
Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options...
March 18, 2017: Oral Oncology
https://www.readbyqxmd.com/read/28325607/japanese-clinical-practice-guideline-for-head-and-neck-cancer
#6
REVIEW
Ken-Ichi Nibu, Ryuichi Hayashi, Takahiro Asakage, Hiroya Ojiri, Yoshihiro Kimata, Takeshi Kodaira, Toshitaka Nagao, Torahiko Nakashima, Takashi Fujii, Hirofumi Fujii, Akihiro Homma, Kazuto Matsuura, Nobuya Monden, Takeshi Beppu, Nobuhiro Hanai, Tadaaki Kirita, Yuzuru Kamei, Naoki Otsuki, Naomi Kiyota, Sadamoto Zenda, Ken Omura, Koichi Omori, Tetsuo Akimoto, Kazuyoshi Kawabata, Seiji Kishimoto, Hiroya Kitano, Iwai Tohnai, Takashi Nakatsuka
OBJECTIVE: The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. METHODS: 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee...
March 18, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28325214/antibody-based-cancer-therapy-successful-agents-and-novel-approaches
#7
D Hendriks, G Choi, M de Bruyn, V R Wiersma, E Bremer
Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#8
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28320945/three-dimensional-culture-system-identifies-a-new-mode-of-cetuximab-resistance-and-disease-relevant-genes-in-colorectal-cancer
#9
Cunxi Li, Bhuminder Singh, Ramona Graves-Deal, Haiting Ma, Alina Starchenko, William H Fry, Yuanyuan Lu, Yang Wang, Galina Bogatcheva, Mohseen P Khan, Ginger L Milne, Shilin Zhao, Gregory Daniel Ayers, Nenggan Li, Huaying Hu, Mary Kay Washington, Timothy J Yeatman, Oliver G McDonald, Qi Liu, Robert J Coffey
We previously reported that single cells from a human colorectal cancer (CRC) cell line (HCA-7) formed either hollow single-layered polarized cysts or solid spiky masses when plated in 3D in type-I collagen. To begin in-depth analyses into whether clonal cysts and spiky masses possessed divergent properties, individual colonies of each morphology were isolated and expanded. The lines thus derived faithfully retained their parental cystic and spiky morphologies and were termed CC (cystic) and SC (spiky), respectively...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28315228/clinical-value-of-monoclonal-antibodies-and-tyrosine-kinase-inhibitors-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#10
REVIEW
Wiktoria Blaszczak, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28314295/development-and-applicability-of-integrative-tumor-response-assays-for-metastatic-colorectal-cancer
#11
Yong Sik Yoon, Chan Wook Kim, Seon Ae Roh, Dong Hyung Cho, Tae Won Kim, Moon Bo Kim, Jin Cheon Kim
AIM: The present study investigated how well the results of integrative tumor-response assay (ITRA) compared to those of clinical response to chemotherapy in patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: A total of 129 patients with metastatic CRC were prospectively enrolled. ITRA consisted of two sequential histoculture drug-response assays (HDRAs). First-stage HDRAs were performed using 5-fluorouracil with leucovorin and oxaliplatin (FX), or with irinotecan (FR)...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303530/a-randomized-open-label-multicenter-phase-ii-study-evaluating-the-efficacy-and-safety-of-bth1677-1-3-1-6-beta-glucan-imprime-pgg-in-combination-with-cetuximab-and-chemotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#12
M Thomas, P Sadjadian, J Kollmeier, J Lowe, P Mattson, J R Trout, M Gargano, M L Patchen, R Walsh, M Beliveau, J F Marier, N Bose, K Gorden, F Schneller
Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m(2) and subsequent doses 250 mg/m(2), weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m(2), Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above)...
March 16, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28301591/in-vivo-and-ex-vivo-cetuximab-sensitivity-assay-using-three-dimensional-primary-culture-system-to-stratify-kras-mutant-colorectal-cancer
#13
Takahiro Tashiro, Hiroaki Okuyama, Hiroko Endo, Kenji Kawada, Yasuko Ashida, Masayuki Ohue, Yoshiharu Sakai, Masahiro Inoue
In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants)...
2017: PloS One
https://www.readbyqxmd.com/read/28289659/single-center-experience-with-hyperthermic-intraperitoneal-chemotherapy
#14
Woo Ram Kim, Hyuk Hur, Byung Soh Min, Seung Hyuk Baik, Kang Young Lee, Nam Kyu Kim
PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed for controlling peritoneal seeding metastasis in some kinds of cancers, including those of colorectal origin, but their safety and oncological benefits are subjects of debate. We present our early experience with those procedures. METHODS: Data were retrospectively collected from all patients with peritoneal carcinomatosis (PC) and pseudomyxoma peritonei (PMP) treated using CRS and HIPEC at Yonsei Cancer Center between July 2014 and July 2015...
February 2017: Annals of Coloproctology
https://www.readbyqxmd.com/read/28288572/a-multi-center-phase-ii-study-and-biomarker-analysis-of-combined-cetuximab-and-modified-folfiri-as-second-line-treatment-in-patients-with-metastatic-gastric-cancer
#15
Xin Liu, Weijian Guo, Wen Zhang, Jiliang Yin, Jun Zhang, Xiaodong Zhu, Tianshu Liu, Zhiyu Chen, Biyun Wang, Jianhua Chang, Fangfang Lv, Xiaonan Hong, Huijie Wang, Jialei Wang, Xinmin Zhao, Xianghua Wu, Jin Li
BACKGROUND: To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes. METHODS: All 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m(2)) and weekly doses (250 mg/m(2)) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m(2)), leucovorin (200 mg/m(2)), and an IV bolus dose of 5-FU (400 mg/m(2)) followed by a continuous infusion of 5-FU (2400 mg/m(2)) for 46 h...
March 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#16
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28284171/molecular-subtypes-of-metastatic-colorectal-cancer-are-associated-with-patient-response-to-irinotecan-based-therapies
#17
M Del Rio, C Mollevi, F Bibeau, N Vie, J Selves, J-F Emile, P Roger, C Gongora, J Robert, N Tubiana-Mathieu, M Ychou, P Martineau
BACKGROUND: Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. PATIENTS AND METHODS: We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment...
March 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28283541/comprehensive-pharmacogenetic-profiling-of-the-epidermal-growth-factor-receptor-pathway-for-biomarkers-of-response-to-and-toxicity-from-cetuximab
#18
Ayman Madi, David Fisher, Timothy S Maughan, James P Colley, Angela M Meade, Sabine Tejpar, Ben Van den Bosch, Julie Maynard, Vikki Humphreys, Harpreet Wasan, Richard A Adams, Shelley Idziaszczyk, Rebecca Harris, Richard S Kaplan, Jeremy P Cheadle
BACKGROUND: Somatic mutations in the epidermal growth factor receptor (EGFR) intracellular signalling pathways predict non-response to cetuximab in the treatment of advanced colorectal cancer (aCRC). We hypothesised that common germline variants within these pathways may also play similar roles. METHODS: We analysed 54 potentially functional, common, inherited EGFR pathway variants in 815 patients with aCRC treated with oxaliplatin-fluoropyrimidine chemotherapy plus cetuximab...
March 10, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#19
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#20
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
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