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

    Vemurafenib resistance reprograms melanoma cells towards glutamine dependence

    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...

    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

    Journal of Translational Medicine 2015 13:210

    Published on: 3 July 2015

  2. Research

    Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine

    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...

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

    Journal of Translational Medicine 2014 12:294

    Published on: 13 November 2014

  3. Research

    Neoadjuvant anti-tumor vaccination prior to surgery enhances survival

    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.

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

    Journal of Translational Medicine 2014 12:245

    Published on: 4 September 2014

  4. Research

    Bioenergetic modulation with dichloroacetate reduces the growth of melanoma cells and potentiates their response to BRAFV600E inhibition

    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 ...

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

    Journal of Translational Medicine 2014 12:247

    Published on: 3 September 2014

  5. Research

    High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors

    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...

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

    Journal of Translational Medicine 2014 12:225

    Published on: 21 August 2014

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

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