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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 enrich the communication between basic biological and immunological sciences and the clinical investigation arena.

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. Our goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progeni...

    Authors: Luisa Corral, Casimiro Javierre, Juan Blasi, Ginés Viscor, Antoni Ricart and Josep Lluis Ventura
    Citation: Journal of Translational Medicine 2014 12:174
  29. The methylation inhibitor 5-Aza-2′-deoxycytidine (decitabine, DAC) has a great therapeutic value for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). But decitabine monotherapy was associated ...

    Authors: Kongfei Li, Chao Hu, Chen Mei, Zhigang Ren, Juan Carlos Vera, Zhengping Zhuang, Jie Jin and Hongyan Tong
    Citation: Journal of Translational Medicine 2014 12:167
  30. Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).

    Authors: Maria Colombino, MariaCristina Sini, Amelia Lissia, Vincenzo De Giorgi, Ignazio Stanganelli, Fabrizio Ayala, Daniela Massi, Corrado Rubino, Antonella Manca, Panagiotis Paliogiannis, Susanna Rossari, Serena Magi, Laura Mazzoni, Gerardo Botti, Mariaelena Capone, Marco Palla…
    Citation: Journal of Translational Medicine 2014 12:117
  31. Glioblastoma (GBM) is a therapeutic challenge, associated with high mortality. More effective GBM therapeutic options are urgently needed. Hence, we screened a large multi-class drug panel comprising the NIH c...

    Authors: Pengfei Jiang, Rajesh Mukthavavam, Ying Chao, Ila Sri Bharati, Valentina Fogal, Sandra Pastorino, Xiuli Cong, Natsuko Nomura, Matt Gallagher, Taher Abbasi, Shireen Vali, Sandeep C Pingle, Milan Makale and Santosh Kesari
    Citation: Journal of Translational Medicine 2014 12:13

    The Erratum to this article has been published in Journal of Translational Medicine 2014 12:126

  32. This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury.

    Authors: Yen-Ta Chen, Tzu-Hsien Tsai, Chih-Chau Yang, Cheuk-Kwan Sun, Li-Teh Chang, Hung-Hwa Chen, Chia-Lo Chang, Pei-Hsun Sung, Yen-Yi Zhen, Steve Leu, Hsueh-Wen Chang, Yung-Lung Chen and Hon-Kan Yip
    Citation: Journal of Translational Medicine 2013 11:270
  33. Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects...

    Authors: Stefano Ferrari, Francesca Perut, Franca Fagioli, Adalberto Brach Del Prever, Cristina Meazza, Antonina Parafioriti, Piero Picci, Marco Gambarotti, Sofia Avnet, Nicola Baldini and Stefano Fais
    Citation: Journal of Translational Medicine 2013 11:268
  34. Homoharringtonine (HHT) is a kind of cephalotaxus alkaloid used in traditional Chinese medicine. Although HHT has been successfully used as a therapeutic agent for leukemia, the drug resistance and toxicity ar...

    Authors: MinRan Zhou, JiPing Zeng, XiaoMing Wang, Qing Guo, Tao Huang, HaiYu Shen, Yue Fu, LiXiang Wang, JiHui Jia and ChunYan Chen
    Citation: Journal of Translational Medicine 2013 11:265
  35. 5-fluorouracil (5-FU) and cisplatin (CDDP) are used to enhance radiotherapy (RT) effect for head and neck (HN) cancers. However, the effect of local RT on systemic chemotherapeutics remains unclear. Here, we e...

    Authors: Chen-Hsi Hsieh, Mei-Ling Hou, Meng-Hsuan Chiang, Hung-Chi Tai, Hui-Ju Tien, Li-Ying Wang, Tung-Hu Tsai and Yu-Jen Chen
    Citation: Journal of Translational Medicine 2013 11:231
  36. This study was to investigate the effects and safety of cathepsin B-cleavable doxorubicin (DOX)-prodrug (PDOX) for targeting therapy of metastatic human hepatocellular carcinoma (HCC) using DOX as a positive c...

    Authors: Qun Wang, Yan-Jun Zhong, Jing-Ping Yuan, Li-Hua Shao, Jue Zhang, Li Tang, Shao-Ping Liu, Ya-Ping Hong, Raymond A Firestone and Yan Li
    Citation: Journal of Translational Medicine 2013 11:192
  37. Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors. However, a limitation to such treatment is the occurrence of resistance. Several mechanisms have been identified to be r...

    Authors: Luigi Fattore, Emanuele Marra, Maria Elena Pisanu, Alessia Noto, Claudia de Vitis, Francesca Belleudi, Luigi Aurisicchio, Rita Mancini, Maria Rosaria Torrisi, Paolo Antonio Ascierto and Gennaro Ciliberto
    Citation: Journal of Translational Medicine 2013 11:180
  38. Cancer vaccines are considered a promising therapeutic approach. However, their clinical results are not yet satisfactory. This may be due to the the difficulty of selection of an efficient tumor associated an...

    Authors: Francesca Kalli, Rodolfo Machiorlatti, Florinda Battaglia, Alessia Parodi, Giuseppina Conteduca, Francesca Ferrera, Michele Proietti, Samuele Tardito, Marina Sanguineti, Enrico Millo, Daniela Fenoglio, Raffaele De Palma, Giorgio Inghirami and Gilberto Filaci
    Citation: Journal of Translational Medicine 2013 11:120
  39. Diabetes mellitus is affecting more than 300 million people worldwide. Current treatment strategies cannot prevent secondary complications. Stem cells due to their regenerative power have long been the attract...

    Authors: Muhammad Tariq, Muhammad Sharif Masoud, Azra Mehmood, Shaheen N Khan and Sheikh Riazuddin
    Citation: Journal of Translational Medicine 2013 11:115
  40. DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols...

    Authors: Claudia Marcela Diaz, Alberto Chiappori, Luigi Aurisicchio, Ansuman Bagchi, Jason Clark, Sheri Dubey, Arthur Fridman, Jesus C Fabregas, John Marshall, Elisa Scarselli, Nicola La Monica, Gennaro Ciliberto and Alberto J Montero
    Citation: Journal of Translational Medicine 2013 11:62
  41. Ipilimumab, an anti-CTLA-4 monoclonal antibody, has been shown to improve overall survival in patients with metastatic melanoma. Preliminary data suggest that patients who fail BRAF inhibitor treatment experie...

    Authors: Paolo Antonio Ascierto, Ester Simeone, Antonio Maria Grimaldi, Marcello Curvietto, Assunta Esposito, Giuseppe Palmieri and Nicola Mozzillo
    Citation: Journal of Translational Medicine 2013 11:61
  42. The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized 2x2 facto...

    Authors: Antonio Daponte, Simona Signoriello, Luigi Maiorino, Bruno Massidda, Ester Simeone, Antonio Maria Grimaldi, Corrado Caracò, Giuseppe Palmieri, Antonio Cossu, Gerardo Botti, Antonella Petrillo, Secondo Lastoria, Ernesta Cavalcanti, Pasquale Aprea, Nicola Mozzillo, Ciro Gallo…
    Citation: Journal of Translational Medicine 2013 11:38
  43. To mimic clinical treatment situations in advanced human ovarian disease, we tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to i...

    Authors: Michele Sommariva, Michelandrea de Cesare, Alessandra Meini, Alessandra Cataldo, Nadia Zaffaroni, Elda Tagliabue and Andrea Balsari
    Citation: Journal of Translational Medicine 2013 11:25
  44. Membrane-bound phospholipid scramblase 1 (PLSCR1) is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas (CRCs). In the prese...

    Authors: Chung-Wei Fan, Chun-Yu Chen, Kuei-Tien Chen, Chia-Rui Shen, Yung-Bin Kuo, Ya-Shan Chen, Yeh-Pin Chou, Wei-Shan Wei and Err-Cheng Chan
    Citation: Journal of Translational Medicine 2012 10:254
  45. Most DNA-damaging chemotherapeutic agents activate the transcription factor nuclear factor κB (NF-κB). However, NF-κB activation can either protect from or contribute to the growth suppressive effects of the a...

    Authors: Simona Caporali, Lauretta Levati, Grazia Graziani, Alessia Muzi, Maria Grazia Atzori, Enzo Bonmassar, Giuseppe Palmieri, Paolo A Ascierto and Stefania D’Atri
    Citation: Journal of Translational Medicine 2012 10:252
  46. The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our...

    Authors: Consolación Melguizo, Jose Prados, Beatriz González, Raul Ortiz, Angel Concha, Pablo Juan Alvarez, Roberto Madeddu, Gloria Perazzoli, Jaime Antonio Oliver, Rodrigo López, Fernando Rodríguez-Serrano and Antonia Aránega
    Citation: Journal of Translational Medicine 2012 10:250
  47. The vast majority of patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab eventually develop resistance to this agent. There is an unmet need therefore, for identifying biologica...

    Authors: George Fountzilas, Christos Christodoulou, Mattheos Bobos, Vassiliki Kotoula, Anastasia G Eleftheraki, Ioannis Xanthakis, Anna Batistatou, George Pentheroudakis, Nikolaos Xiros, Irene Papaspirou, Anna Koumarianou, Pavlos Papakostas, Dimitrios Bafaloukos, Dimosthenis V Skarlos and Konstantine T Kalogeras
    Citation: Journal of Translational Medicine 2012 10:212
  48. The concept of tissue banking as a “bio-repository” aimed to collection, storing and distribution of human biological material and clinical information, is emerging as a successful strategy to support clinical...

    Authors: Gerardo Botti, Renato Franco, Monica Cantile, Gennaro Ciliberto and Paolo Antonio Ascierto
    Citation: Journal of Translational Medicine 2012 10:204

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