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.

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  1. Research

    AurkA inhibitors enhance the effects of B-RAF and MEK inhibitors in melanoma treatment

    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.

    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

    Journal of Translational Medicine 2014 12:216

    Published on: 31 July 2014

  2. Meeting report

    Routing cancer immunology and immunotherapy from the lab to the clinic 4–5 th March 2014, Center for Applied Medical Research and University Clinic, Pamplona, Spain

    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...

    M Ángela Aznar, Ignacio Melero and José I Quetglas

    Journal of Translational Medicine 2014 12:202

    Published on: 24 July 2014

  3. Research

    Combination treatment with oncolytic Vaccinia virus and cyclophosphamide results in synergistic antitumor effects in human lung adenocarcinoma bearing mice

    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...

    Elisabeth Hofmann, Stephanie Weibel and Aladar A Szalay

    Journal of Translational Medicine 2014 12:197

    Published on: 17 July 2014

  4. Methodology

    Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

    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...

    Luisa Corral, Casimiro Javierre, Juan Blasi, Ginés Viscor, Antoni Ricart and Josep Lluis Ventura

    Journal of Translational Medicine 2014 12:174

    Published on: 19 June 2014

  5. Research

    Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target

    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 ...

    Kongfei Li, Chao Hu, Chen Mei, Zhigang Ren, Juan Carlos Vera, Zhengping Zhuang, Jie Jin and Hongyan Tong

    Journal of Translational Medicine 2014 12:167

    Published on: 12 June 2014

  6. Research

    Discrepant alterations in main candidate genes among multiple primary melanomas

    Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).

    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…

    Journal of Translational Medicine 2014 12:117

    Published on: 8 May 2014

  7. Research

    Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs

    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...

    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

    Journal of Translational Medicine 2014 12:13

    Published on: 17 January 2014

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

  8. Research

    Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction

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

    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

    Journal of Translational Medicine 2013 11:270

    Published on: 25 October 2013

  9. Research

    Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients’ bed

    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...

    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

    Journal of Translational Medicine 2013 11:268

    Published on: 24 October 2013

  10. Research

    MiR-370 sensitizes chronic myeloid leukemia K562 cells to homoharringtonine by targeting Forkhead box M1

    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...

    MinRan Zhou, JiPing Zeng, XiaoMing Wang, Qing Guo, Tao Huang, HaiYu Shen, Yue Fu, LiXiang Wang, JiHui Jia and ChunYan Chen

    Journal of Translational Medicine 2013 11:265

    Published on: 23 October 2013

  11. Research

    Head and neck irradiation modulates pharmacokinetics of 5-fluorouracil and cisplatin

    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...

    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

    Journal of Translational Medicine 2013 11:231

    Published on: 26 September 2013

  12. Research

    Targeting therapy of hepatocellular carcinoma with doxorubicin prodrug PDOX increases anti-metastatic effect and reduces toxicity: a preclinical study

    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...

    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

    Journal of Translational Medicine 2013 11:192

    Published on: 21 August 2013

  13. Research

    Activation of an early feedback survival loop involving phospho-ErbB3 is a general response of melanoma cells to RAF/MEK inhibition and is abrogated by anti-ErbB3 antibodies

    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...

    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

    Journal of Translational Medicine 2013 11:180

    Published on: 27 July 2013

  14. Research

    Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice

    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...

    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

    Journal of Translational Medicine 2013 11:120

    Published on: 12 May 2013

  15. Research

    Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in-vitro and ameliorates drug induced diabetes in rats

    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...

    Muhammad Tariq, Muhammad Sharif Masoud, Azra Mehmood, Shaheen N Khan and Sheikh Riazuddin

    Journal of Translational Medicine 2013 11:115

    Published on: 6 May 2013

  16. Commentary

    Do BRAF inhibitors select for populations with different disease progression kinetics?

    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...

    Paolo Antonio Ascierto, Ester Simeone, Antonio Maria Grimaldi, Marcello Curvietto, Assunta Esposito, Giuseppe Palmieri and Nicola Mozzillo

    Journal of Translational Medicine 2013 11:61

    Published on: 8 March 2013

  17. Research

    Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors

    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...

    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

    Journal of Translational Medicine 2013 11:62

    Published on: 8 March 2013

  18. Protocol

    Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma

    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...

    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…

    Journal of Translational Medicine 2013 11:38

    Published on: 13 February 2013

  19. Research

    High efficacy of CpG-ODN, Cetuximab and Cisplatin combination for very advanced ovarian xenograft tumors

    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...

    Michele Sommariva, Michelandrea de Cesare, Alessandra Meini, Alessandra Cataldo, Nadia Zaffaroni, Elda Tagliabue and Andrea Balsari

    Journal of Translational Medicine 2013 11:25

    Published on: 29 January 2013

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