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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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

    The Correction to this article has been published in Journal of Translational Medicine 2020 18:212

  11. 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

    The Correction to this article has been published in Journal of Translational Medicine 2021 19:407

  12. 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
  13. 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

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

  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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

  45. 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
  46. 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
  47. 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
  48. 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

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