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Combination strategies

Section edited by Paolo A. Ascierto

This section aims to provide a focal point for research that highlights combination therapies, where two or more medications or therapies are strategically combined to improve the treatment of cancer, chronic infections, transplantation and potentially other complex and multi-factorial diseases.

Increasingly detailed understanding of the molecular basis driving complex disease has led to the identifications of new agents that target specific pathways. In some cases treatment of appropriately selected patients has led to striking clinical response, however both primary and secondary resistance mechanisms limited the success of many of these agents. It has become clear that combining or sequencing treatment modalities may en to enrich the communication between basic biological and immunological sciences and the clinical investigation arena.

Featured articles

Suppression of RAF/MEK or PI3K synergizes cytotoxicity of receptor tyrosine kinase inhibitors in glioma tumor-initiating cells
Takashi Shingu, et al


Vemurafenib resistance reprograms melanoma cells towards glutamine dependence
Jenny E Hernandez-Davies, et al


What’s new in melanoma? Combination!
Paolo A Ascierto, Francesco M Marincola and Michael B Atkins

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  1. Content type: Research

    The roles played by cholesterol in cancer development and progression represent a popular field in the cancer community. High cholesterol levels are positively correlated with the risk of various types of canc...

    Authors: Tao Zhang, Qilong Wang, Yeqi Wang, Junping Wang, Yongping Su, Fengchao Wang and Guixue Wang

    Citation: Journal of Translational Medicine 2019 17:161

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  2. Content type: Meeting report

    The great debate session at the 2018 Melanoma Bridge congress (November 29–December 1, Naples, Italy) featured counterpoint views from experts on three topical issues in melanoma. These were whether overall su...

    Authors: Paolo A. Ascierto, Paolo Bruzzi, Alexander Eggermont, Omid Hamid, Hussein A. Tawbi, Alexander van Akkooi, Alessandro Testori, Corrado Caracò, Igor Puzanov and Francesco Perrone

    Citation: Journal of Translational Medicine 2019 17:148

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  3. Content type: Research

    There are no accepted universal biomarkers capable to accurately predict response to immuno-checkpoint inhibitors (ICI). Although recent literature has been flooded with studies on ICI predictive biomarkers, a...

    Authors: Matteo Pallocca, Davide Angeli, Fabio Palombo, Francesca Sperati, Michele Milella, Frauke Goeman, Francesca De Nicola, Maurizio Fanciulli, Paola Nisticò, Concetta Quintarelli and Gennaro Ciliberto

    Citation: Journal of Translational Medicine 2019 17:131

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  4. Content type: Research

    Stereotactic ablative radiotherapy (SABR) shows a remarkable local control of non-small cell lung cancer (NSCLC) metastases, partially as a result of host immune status. However, the predictors of immune cells...

    Authors: Chao Liu, Qinyong Hu, Kai Hu, Huichao Su, Fang Shi, Li Kong, Hui Zhu and Jinming Yu

    Citation: Journal of Translational Medicine 2019 17:120

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  5. Content type: Research

    With increasing number of breast cancer survivors, more attention is drawn to long-term consequences of curative cancer treatment. Adjuvant treatment of breast cancer patients is associated with several unfavo...

    Authors: Stine Overvad Fredslund, Claus Højbjerg Gravholt, Britt Elmedal Laursen and Anders Bonde Jensen

    Citation: Journal of Translational Medicine 2019 17:105

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  6. Content type: Research

    The advent of immune checkpoint inhibitors (ICIs) has considerably expanded the armamentarium against non-small cell lung cancer (NSCLC) contributing to reshaping treatment paradigms in the advanced disease se...

    Authors: Andrea Botticelli, Massimiliano Salati, Francesca Romana Di Pietro, Lidia Strigari, Bruna Cerbelli, Ilaria Grazia Zizzari, Raffaele Giusti, Marco Mazzotta, Federica Mazzuca, Michela Roberto, Patrizia Vici, Laura Pizzuti, Marianna Nuti and Paolo Marchetti

    Citation: Journal of Translational Medicine 2019 17:99

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  7. Content type: Research

    A clinical diagnosis model include thyroid functions, thyroid antibodies and radioactive iodine uptake (RAIU) of patients with hyperthyroidism were established and as new evaluation indicators for the differen...

    Authors: Zhaohui Cui, Zhixiao Wang, Xiaoyun Liu, Yun Cai, Xinyu Xu and Tao Yang

    Citation: Journal of Translational Medicine 2019 17:11

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  8. Content type: Research

    Neurogenin3 (Ngn3) and neurogenic differentiation 1 (NeuroD1), two crucial transcriptional factors involved in human diabetes (OMIM: 601724) and islet development, have been previously found to directly target...

    Authors: Lin Wang, Zhong Sheng Sun, Bingwu Xiang, Chi-ju Wei, Yan Wang, Kevin Sun, Guanjie Chen, Michael S. Lan, Gilberto N. Carmona, Abner L. Notkins and Tao Cai

    Citation: Journal of Translational Medicine 2018 16:297

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  9. Content type: Research

    The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor due to the difficulty of disease diagnosis and therapy. Immunotherapy has had robust performance against several malignancies, including PD...

    Authors: Ning Pu, Guochao Zhao, Hanlin Yin, Jian-ang Li, Abulimiti Nuerxiati, Dansong Wang, Xuefeng Xu, Tiantao Kuang, Dayong Jin, Wenhui Lou and Wenchuan Wu

    Citation: Journal of Translational Medicine 2018 16:294

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  10. Content type: Protocol

    Ruptured aneurysms, the commonest cause of nontraumatic subarachnoid hemorrhage, can be catastrophic; the mortality and morbidity of affected patients being very high. Some risk factors, such as smoking, hyper...

    Authors: Junfan Chen, Jian Liu, Yisen Zhang, Zhongbin Tian, Kun Wang, Ying Zhang, Shiqing Mu, Ming Lv, Peng Jiang, ChuanZhi Duan, Hongqi Zhang, Yan Qu, Min He and Xinjian Yang

    Citation: Journal of Translational Medicine 2018 16:263

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  11. Content type: Research

    Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth ...

    Authors: Dan-dan Xiong, Yi-wu Dang, Peng Lin, Dong-yue Wen, Rong-quan He, Dian-zhong Luo, Zhen-bo Feng and Gang Chen

    Citation: Journal of Translational Medicine 2018 16:220

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  12. Content type: Research

    Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patie...

    Authors: Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Massimiliano Salati, Annalinda Pisano, Mazzuca Federica, Maurizio Simmaco, Marianna Nuti and Paolo Marchetti

    Citation: Journal of Translational Medicine 2018 16:219

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  13. Content type: Research

    Endoplasmic reticulum (ER) stress and its consequent unfolded protein response (UPR) are believed to be associated with progression, survival and chemoresistance of a variety of tumor cells through multiple ce...

    Authors: Prakash C. Thakur, Jennifer L. Miller-Ocuin, Khanh Nguyen, Rina Matsuda, Aatur D. Singhi, Herbert J. Zeh and Nathan Bahary

    Citation: Journal of Translational Medicine 2018 16:190

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  14. Content type: Research

    Clinical trials have shown combinations of anti–tumor necrosis factor biologicals plus methotrexate (MTX) are more effective treatments for rheumatoid arthritis than biological monotherapies, based, in part, o...

    Authors: Alison O’Mahony, Markus R. John, Hannah Cho, Misato Hashizume and Ernest H. Choy

    Citation: Journal of Translational Medicine 2018 16:156

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  15. Content type: Research

    The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patien...

    Authors: Yanan Jiang, Jimin Zhao, Yi Zhang, Ke Li, Tiepeng Li, Xinhuan Chen, Simin Zhao, Song Zhao, Kangdong Liu and Ziming Dong

    Citation: Journal of Translational Medicine 2018 16:138

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  16. Content type: Research

    Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonis...

    Authors: Xiaodong Wang, Yu Liu, Yuwen Diao, Ningning Gao, Yanyan Wan, Jingjing Zhong, Huali Zheng, Zhulin Wang and Guangyi Jin

    Citation: Journal of Translational Medicine 2018 16:120

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  17. Content type: Research

    Ischemia–reperfusion (I/R)-induced acute kidney injury (AKI) not only prolongs the length of hospital stay, but also seriously affects the patient’s survival rate. Although our previous investigation has verif...

    Authors: Yu Gu, Fei Huang, Yanling Wang, Chaojin Chen, Shan Wu, Shaoli Zhou, Ziqing Hei and Dongdong Yuan

    Citation: Journal of Translational Medicine 2018 16:117

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  18. Content type: Research

    Radiotherapy constitutes a standard arm of therapy in the multimodal treatment of patients with glioblastoma (GBM). Ironically, studies have recently revealed that radiation can augment malignant progression, ...

    Authors: Xin Zhang, Xuehai Wang, Ran Xu, Jianxiong Ji, Yangyang Xu, Mingzhi Han, Yuzhen Wei, Bin Huang, Anjing Chen, Qing Zhang, Wenjie Li, Jian Wang, Xingang Li and Chen Qiu

    Citation: Journal of Translational Medicine 2018 16:79

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  19. Content type: Meeting report

    Major advances have been made in the treatment of cancer with targeted therapy and immunotherapy; several FDA-approved agents with associated improvement of 1-year survival rates became available for stage IV ...

    Authors: Paolo A. Ascierto, Sanjiv S. Agarwala, Gennaro Ciliberto, Sandra Demaria, Reinhard Dummer, Connie P. M. Duong, Soldano Ferrone, Silvia C. Formenti, Claus Garbe, Ruth Halaban, Samir Khleif, Jason J. Luke, Lluis M. Mir, Willem W. Overwijk, Michael Postow, Igor Puzanov…

    Citation: Journal of Translational Medicine 2017 15:236

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  20. Content type: Research

    Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality...

    Authors: Maria A. Pizzichetta, Daniela Massi, Mario Mandalà, Paola Queirolo, Ignazio Stanganelli, Vincenzo De Giorgi, Giovanni Ghigliotti, Stefano Cavicchini, Pietro Quaglino, Maria T. Corradin, Pietro Rubegni, Mauro Alaibac, Stefano Astorino, Fabrizio Ayala, Serena Magi, Laura Mazzoni…

    Citation: Journal of Translational Medicine 2017 15:227

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    The Correction to this article has been published in Journal of Translational Medicine 2018 16:33

  21. Content type: Protocol

    Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in ...

    Authors: Nora Sundahl, Katrien De Wolf, Sylvie Rottey, Karel Decaestecker, Daan De Maeseneer, Annabel Meireson, Els Goetghebeur, Valérie Fonteyne, Sofie Verbeke, Pieter De Visschere, Dries Reynders, Mireille Van Gele, Lieve Brochez and Piet Ost

    Citation: Journal of Translational Medicine 2017 15:150

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  22. Content type: Research

    Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be con...

    Authors: Gianluca Di Monta, Corrado Caracò, Ester Simeone, Antonio Maria Grimaldi, Ugo Marone, Massimiliano Di Marzo, Vito Vanella, Lucia Festino, Marco Palla, Stefano Mori, Nicola Mozzillo and Paolo Antonio Ascierto

    Citation: Journal of Translational Medicine 2017 15:82

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  23. Content type: Research

    Diminished wound healing is a major complication of diabetes mellitus and can lead to foot ulcers. However, there are limited therapeutic methods to treat this condition. Exendin-4 (Ex-4), a glucagon-like pept...

    Authors: Eunhui Seo, Jae Soo Lim, Jin-Bum Jun, Woohyuk Choi, In-Sun Hong and Hee-Sook Jun

    Citation: Journal of Translational Medicine 2017 15:35

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  24. Content type: Research

    Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and th...

    Authors: Li Li, Wei Wang, Hong Pan, Ge Ma, Xinyi Shi, Hui Xie, Xiaoan Liu, Qiang Ding, Wenbin Zhou and Shui Wang

    Citation: Journal of Translational Medicine 2017 15:23

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  25. Content type: Protocol

    Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regula...

    Authors: Katrien De Wolf, Vibeke Kruse, Nora Sundahl, Mireille van Gele, Ines Chevolet, Reinhart Speeckaert, Lieve Brochez and Piet Ost

    Citation: Journal of Translational Medicine 2017 15:21

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  26. Content type: Commentary

    The occurrence of high rates of somatic mutations in cancer is believed to correspond to increased frequency of neo-epitope formation and tumor immunogenicity. Thus, classification of patients with cancer acco...

    Authors: Giuseppe Palmieri, Maria Colombino, Antonio Cossu, Antonio Marchetti, Gerardo Botti and Paolo A. Ascierto

    Citation: Journal of Translational Medicine 2017 15:17

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  27. Content type: Commentary

    Expression of the platelet-activating factor receptor is upregulated in the respiratory epithelium of smokers and chronic obstructive pulmonary disease patients. We have recently determined that increased expr...

    Authors: Ronan F. O’Toole, Shakti D. Shukla and Eugene H. Walters

    Citation: Journal of Translational Medicine 2016 14:304

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  28. Content type: Research

    Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS,...

    Authors: Grazia Palomba, Valentina Doneddu, Antonio Cossu, Panagiotis Paliogiannis, Antonella Manca, Milena Casula, Maria Colombino, Annamaria Lanzillo, Efisio Defraia, Antonio Pazzola, Giovanni Sanna, Carlo Putzu, Salvatore Ortu, Mario Scartozzi, Maria Teresa Ionta, Giovanni Baldino…

    Citation: Journal of Translational Medicine 2016 14:292

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  29. Content type: Review

    Despite standard treatment for epithelial ovarian cancer (EOC), that involves cytoreductive surgery followed by platinum-based chemotherapy, and initial high response rates to these, up to 80 % of patients exp...

    Authors: Anselmo Papa, Davide Caruso, Martina Strudel, Silverio Tomao and Federica Tomao

    Citation: Journal of Translational Medicine 2016 14:267

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  30. Content type: Research

    Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no esta...

    Authors: Emmanuel Fenouillet, Aude Vigouroux, Jean Guillaume Steinberg, Alexandre Chagvardieff, Frédérique Retornaz, Regis Guieu and Yves Jammes

    Citation: Journal of Translational Medicine 2016 14:251

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  31. Content type: Research

    Experimentally, lung inflammation in laboratory animals is usually detected by the presence of inflammatory markers, such as immune cells and cytokines, in the bronchoalveolar lavage fluid (BALF) of sacrificed...

    Authors: Fabio Stellari, Gabriella Bergamini, Francesca Ruscitti, Angela Sandri, Francesca Ravanetti, Gaetano Donofrio, Federico Boschi, Gino Villetti, Claudio Sorio, Barouk M. Assael, Paola Melotti and Maria M. Lleo

    Citation: Journal of Translational Medicine 2016 14:226

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  32. Content type: Research

    Tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally identified to show potent anti-tumor activity and immunomodulatory capability. Unfortunately, several clinical studies of relevant...

    Authors: Jing Shen, Zhi Jie Li, Long Fei Li, Lan Lu, Zhan Gang Xiao, William Ka Kei Wu, Lin Zhang, Ming Xing Li, Wei Hu, Kam Ming Chan and Chi Hin Cho

    Citation: Journal of Translational Medicine 2016 14:187

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  33. Content type: Research

    Melanoma is the most lethal type of skin cancer and its incidence is progressively increasing. The introductions of immunotherapy and targeted therapies have tremendously improved the treatment of melanoma. Se...

    Authors: Jurjen Tel, Rutger Koornstra, Nienke de Haas, Vincent van Deutekom, Harm Westdorp, Steve Boudewijns, Nielka van Erp, Stefania Di Blasio, Winald Gerritsen, Carl G. Figdor, I. Jolanda M. de Vries and Stanleyson V. Hato

    Citation: Journal of Translational Medicine 2016 14:88

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  34. Content type: Research

    Synergistic cytotoxicity with high-dose statins and erlotinib has been demonstrated in preclinical models across a number of tumour types. In this phase I study, we evaluated the safety and potential anti-tumo...

    Authors: Glenwood D. Goss, Derek J. Jonker, Scott A. Laurie, Johanne I. Weberpals, Amit M. Oza, Johanna N. Spaans, Charles la Porte and Jim Dimitroulakos

    Citation: Journal of Translational Medicine 2016 14:83

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  35. Content type: Research

    Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especia...

    Authors: Giuseppe Roscilli, Claudia De Vitis, Fabiana Fosca Ferrara, Alessia Noto, Emanuela Cherubini, Alberto Ricci, Salvatore Mariotta, Enrico Giarnieri, Maria Rosaria Giovagnoli, Maria Rosaria Torrisi, Francesca Bergantino, Susan Costantini, Francesca Fenizia, Matilde Lambiase, Luigi Aurisicchio, Nicola Normanno…

    Citation: Journal of Translational Medicine 2016 14:61

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  36. Content type: Research

    Previous studies suggest that certain transition metal complexes, such as cisplatin, are efficacious for treating various cancer types, including ovarian, lung, and breast.

    Authors: Joji Iida, Elisabeth T. Bell-Loncella, Marc L. Purazo, Yifeng Lu, Jesse Dorchak, Rebecca Clancy, Julianna Slavik, Mary Lou Cutler and Craig D. Shriver

    Citation: Journal of Translational Medicine 2016 14:48

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  37. Content type: Research

    The majority of glioblastomas have aberrant receptor tyrosine kinase (RTK)/RAS/phosphoinositide 3 kinase (PI3K) signaling pathways and malignant glioma cells are thought to be addicted to these signaling pathw...

    Authors: Takashi Shingu, Lindsay Holmes, Verlene Henry, Qianghu Wang, Khatri Latha, Anupama E. Gururaj, Laura A. Gibson, Tiffany Doucette, Frederick F. Lang, Ganesh Rao, Liang Yuan, Erik P. Sulman, Nicholas P. Farrell, Waldemar Priebe, Kenneth R. Hess, Yaoqi A. Wang…

    Citation: Journal of Translational Medicine 2016 14:46

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  38. Content type: Research

    Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable pa...

    Authors: Jennifer Johnson, Maria Libera Ascierto, Sandeep Mittal, David Newsome, Liang Kang, Michael Briggs, Kirk Tanner, Francesco M. Marincola, Michael E. Berens, George F. Vande Woude and Qian Xie

    Citation: Journal of Translational Medicine 2015 13:306

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  39. Content type: Editorial

    Melanoma was again a focus of attention at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, in particular the use of combination treatment strategies involving immunotherapies and/or tar...

    Authors: Paolo A Ascierto, Francesco M Marincola and Michael B Atkins

    Citation: Journal of Translational Medicine 2015 13:213

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  40. Content type: Research

    V600 BRAF mutations drive approximately 50% of metastatic melanoma which can be therapeutically targeted by BRAF inhibitors (BRAFi) and, based on resistance mechanisms, the co...

    Authors: Jenny E Hernandez-Davies, Thai Q Tran, Michael A Reid, Kimberly R Rosales, Xazmin H Lowman, Min Pan, Gatien Moriceau, Ying Yang, Jun Wu, Roger S Lo and Mei Kong

    Citation: Journal of Translational Medicine 2015 13:210

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  41. Content type: Research

    Growing awareness of the complexity of carcinogenesis has made multimodal therapies for cancer increasingly compelling and relevant. In recent years, immunotherapy has gained acceptance as an active therapeuti...

    Authors: Anna R Kwilas, Andressa Ardiani, Renee N Donahue, Dana T Aftab and James W Hodge

    Citation: Journal of Translational Medicine 2014 12:294

    Published on:

  42. Content type: Research

    This study was conducted to determine if anti-tumor vaccination administered prior to partial debulking surgery could improve survival using a murine solid tumour model.

    Authors: Scott A Fisher, Amanda Cleaver, Devina D Lakhiani, Andrea Khong, Theresa Connor, Ben Wylie, W Joost Lesterhuis, Bruce WS Robinson and Richard A Lake

    Citation: Journal of Translational Medicine 2014 12:245

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  43. Content type: Research

    Advances in melanoma treatment through targeted inhibition of oncogenic BRAF are limited owing to the development of acquired resistance. The involvement of BRAFV600E in metabolic reprogramming of melanoma cells ...

    Authors: Cecilie Abildgaard, Christina Dahl, Astrid L Basse, Tao Ma and Per Guldberg

    Citation: Journal of Translational Medicine 2014 12:247

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  44. Content type: Research

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification...

    Authors: Enrico P Spugnini, Sabrina Buglioni, Francesca Carocci, Menicagli Francesco, Bruno Vincenzi, Maurizio Fanciulli and Stefano Fais

    Citation: Journal of Translational Medicine 2014 12:225

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  45. Content type: Research

    Aurora kinase A (AurkA) is over-expressed in melanoma and its inhibition has been observed to limit tumor growth, suggesting a potential role in melanoma treatment.

    Authors: Emilia Caputo, Roberta Miceli, Maria Letizia Motti, Rosarita Taté, Federica Fratangelo, Gerardo Botti, Nicola Mozzillo, Maria Vincenza Carriero, Ernesta Cavalcanti, Giuseppe Palmieri, Gennaro Ciliberto, Giuseppe Pirozzi and Paolo Antonio Ascierto

    Citation: Journal of Translational Medicine 2014 12:216

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  46. Content type: Meeting report

    New approaches to generate effective anticancer responses by either inducing immune responses or inhibiting immunosuppression are under development to improve efficacy in patients. On March 4-5th, 2014, a symposi...

    Authors: M Ángela Aznar, Ignacio Melero and José I Quetglas

    Citation: Journal of Translational Medicine 2014 12:202

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  47. Content type: Research

    The capacity of the recombinant Vaccinia virus GLV-1h68 as a single agent to efficiently treat different human or canine cancers has been shown in several preclinical studies. Currently, its human safety and e...

    Authors: Elisabeth Hofmann, Stephanie Weibel and Aladar A Szalay

    Citation: Journal of Translational Medicine 2014 12:197

    Published on:

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