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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. Antibody based cancer therapies have achieved convincing success rates combining enhanced tumor specificity and reduced side effects in patients. Trastuzumab that targets the human epidermal growth factor rela...

    Authors: Anja Kathrin Wege, Nicole Kirchhammer, Linda Veronique Kazandjian, Sandra Prassl, Michael Brandt, Gerhard Piendl, Olaf Ortmann, Stephan Fischer and Gero Brockhoff
    Citation: Journal of Translational Medicine 2020 18:316
  2. Necrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin (EPO) has the...

    Authors: Yong Wang, Juan Song, Huiqing Sun, Falin Xu, Kenan Li, Chunxia Nie, Xiaoli Zhang, Xirui Peng, Lei Xia, Ziyun Shen, Xiao Yuan, Shan Zhang, Xue Ding, Yaodong Zhang, Wenqing Kang, Liling Qian…
    Citation: Journal of Translational Medicine 2020 18:308
  3. We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) o...

    Authors: Paolo A. Ascierto, Antoni Ribas, James Larkin, Grant A. McArthur, Karl D. Lewis, Axel Hauschild, Keith T. Flaherty, Edward McKenna, Qian Zhu, Yong Mun and Brigitte Dréno
    Citation: Journal of Translational Medicine 2020 18:294
  4. Immunotherapy with checkpoint inhibitors (CPI) targeting PD-1 or CTLA-4 has emerged as an important treatment modality for several cancer forms. In hormone receptor positive breast cancer (HR + BC), this thera...

    Authors: J. A. Kyte, N. K. Andresen, H. G. Russnes, S. Ø. Fretland, R. S. Falk, O. C. Lingjærde and B. Naume
    Citation: Journal of Translational Medicine 2020 18:269
  5. The recent global pandemic has placed a high priority on identifying drugs to prevent or lessen clinical infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused by Coronavirus disease...

    Authors: Jason Kim, Jenny Zhang, Yoonjeong Cha, Sarah Kolitz, Jason Funt, Renan Escalante Chong, Scott Barrett, Rebecca Kusko, Ben Zeskind and Howard Kaufman
    Citation: Journal of Translational Medicine 2020 18:257
  6. Immunotherapy with checkpoint inhibitors (CI) represents an important novel development in cancer treatment. Metastatic triple-negative breast cancer (mTNBC) is incurable, with a median survival of only ~ 13 m...

    Authors: J. A. Kyte, A. Røssevold, R. S. Falk and B. Naume
    Citation: Journal of Translational Medicine 2020 18:252
  7. Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs effi...

    Authors: Yue An, Zhonghua Wu, Ningning Wang, Zhidong Yang, Yue Li, Boyang Xu and Mingjun Sun
    Citation: Journal of Translational Medicine 2020 18:235
  8. COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effe...

    Authors: Giovanni Salvatori, Laura Luberto, Mariano Maffei, Luigi Aurisicchio, Giuseppe Roscilli, Fabio Palombo and Emanuele Marra
    Citation: Journal of Translational Medicine 2020 18:222
  9. The outbreak of the novel coronavirus disease 2019 (COVID-19) and consequent social distancing practices have disrupted essential clinical research functions worldwide. Ironically, this coincides with an immed...

    Authors: Iman Osman, Paolo Cotzia, Una Moran, Douglas Donnelly, Carolina Arguelles-Grande, Sandra Mendoza and Andre Moreira
    Citation: Journal of Translational Medicine 2020 18:219

    The Correction to this article has been published in Journal of Translational Medicine 2021 19:240

  10. Immunotherapeutic regulation of the tumor microenvironment in prostate cancer patients is not understood. Most antibody immunotherapies have not succeeded in prostate cancer. We showed previously that high-ris...

    Authors: Stephen T. Ryan, Jing Zhang, Danielle N. Burner, Michael Liss, Emily Pittman, Michelle Muldong, Ahmed Shabaik, Jason Woo, Nicole Basler, Jonathan Cunha, Shabnam Shalapour, Monica V. Estrada, Michael Karin, Karen Messer, Stephen Howell, Christopher J. Kane…
    Citation: Journal of Translational Medicine 2020 18:214

    The Letter to the Editor to this article has been published in Journal of Translational Medicine 2020 18:333

  11. The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become t...

    Authors: Negar Moradian, Hans D. Ochs, Constantine Sedikies, Michael R. Hamblin, Carlos A. Camargo Jr., J. Alfredo Martinez, Jacob D. Biamonte, Mohammad Abdollahi, Pedro J. Torres, Juan J. Nieto, Shuji Ogino, John F. Seymour, Ajith Abraham, Valentina Cauda, Sudhir Gupta, Seeram Ramakrishna…
    Citation: Journal of Translational Medicine 2020 18:205
  12. Most mutations in melanoma affect one critical amino acid on BRAF gene, resulting in the V600E substitution. Patient management is often based on the use of specific inhibitors targeting this mutation.

    Authors: Muna Al Hashmi, Konduru S. Sastry, Lee Silcock, Lotfi Chouchane, Valentina Mattei, Nicola James, Rebecca Mathew, Davide Bedognetti, Valeria De Giorgi, Daniela Murtas, Wei Liu, Aouatef Chouchane, Ramzi Temanni, Barbara Seliger, Ena Wang, Francesco M. Marincola…
    Citation: Journal of Translational Medicine 2020 18:192
  13. The Great Debate session at the 2019 Melanoma Bridge congress (December 5-7, Naples, Italy) featured counterpoint views from experts on five topical issues in melanoma. These were whether to choose local intra...

    Authors: Paolo A. Ascierto, Sanjiv S. Agarwala, Alexander Eggermont, Jeffrey E. Gershenwald, Jean-Jacques Grob, Omid Hamid, Olivier Michielin, Michael Postow, Igor Puzanov, Hassane M. Zarour, Corrado Caracò and Alessandro Testori
    Citation: Journal of Translational Medicine 2020 18:171
  14. Human telomerase reverse transcriptase (hTERT) is an antigen that may represent a target for a novel anti-cancer strategy. A pilot, phase I study tested the safety and feasibility of a prime-boost immunization...

    Authors: Luigi Aurisicchio, Arthur Fridman, David Mauro, Rose Sheloditna, Alberto Chiappori, Ansuman Bagchi and Gennaro Ciliberto
    Citation: Journal of Translational Medicine 2020 18:39
  15. Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint inhibitors has provided promising results, m...

    Authors: Trude G. Simonsen, Jon-Vidar Gaustad and Einar K. Rofstad
    Citation: Journal of Translational Medicine 2020 18:13
  16. Tumor cells have evolved complex strategies to escape immune surveillance, a process which involves NK cells and T lymphocytes, and various immunological factors. Indeed, tumor cells recruit immunosuppressive ...

    Authors: Raquel Alves, Stephanie E. B. McArdle, Jayakumar Vadakekolathu, Ana Cristina Gonçalves, Paulo Freitas-Tavares, Amélia Pereira, Antonio M. Almeida, Ana Bela Sarmento-Ribeiro and Sergio Rutella
    Citation: Journal of Translational Medicine 2020 18:2
  17. Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although i...

    Authors: Sara I. Pai, Ezra E. W. Cohen, Derrick Lin, George Fountzilas, Edward S. Kim, Holger Mehlhorn, Neus Baste, Daniel Clayburgh, Loren Lipworth, Carlo Resteghini, Nawar Shara, Takashi Fujii, Jun Zhang, Michael Stokes, Huifen Wang, Philip Twumasi-Ankrah…
    Citation: Journal of Translational Medicine 2019 17:429
  18. A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to countera...

    Authors: Salvatore Venosi, Giancarlo Ceccarelli, Massimiliano de Angelis, Luca Laghi, Laura Bianchi, Ombretta Martinelli, Debora Maruca, Eugenio Nelson Cavallari, Fabrizia Toscanella, Paolo Vassalini, Vito Trinchieri, Alessandra Oliva and Gabriella d’Ettorre
    Citation: Journal of Translational Medicine 2019 17:364
  19. Magnetic resonance guided focused ultrasound was suggested for the induction of deep localized hyperthermia adjuvant to radiation- or chemotherapy. In this study we are aiming to validate an experimental model...

    Authors: Pauline C. Guillemin, Laura Gui, Orane Lorton, Thomas Zilli, Lindsey A. Crowe, Stéphane Desgranges, Xavier Montet, Sylvain Terraz, Raymond Miralbell, Rares Salomir and Sana Boudabbous
    Citation: Journal of Translational Medicine 2019 17:350
  20. Only few studies, with small patient cohorts, have evaluated the effect of radiotherapy (RT) for metaplastic breast cancer (MBC). Hence, it is important to investigate the role of RT in MBC survival using a la...

    Authors: Yongfeng Li, Meng Chen, Barbara Pardini, Mihnea P. Dragomir, Anthony Lucci and George A. Calin
    Citation: Journal of Translational Medicine 2019 17:318
  21. This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients.

    Authors: Gaetano Facchini, Sabrina Rossetti, Massimiliano Berretta, Carla Cavaliere, Sarah Scagliarini, Maria Giuseppa Vitale, Chiara Ciccarese, Giuseppe Di Lorenzo, Erica Palesandro, Vincenza Conteduca, Umberto Basso, Emanuele Naglieri, Azzurra Farnesi, Michele Aieta, Nicolò Borsellino, Leonardo La Torre…
    Citation: Journal of Translational Medicine 2019 17:296
  22. The skin is impacted by every form of external radiation therapy. However, effective therapeutic options for severe, acute radiation-induced skin reactions are limited. Although platelet-rich plasma (PRP) is k...

    Authors: Janet Lee, Hyosun Jang, Sunhoo Park, Hyunwook Myung, Kyuchang Kim, Hyewon Kim, Won-Suk Jang, Sun-Joo Lee, Jae Kyung Myung and Sehwan Shim
    Citation: Journal of Translational Medicine 2019 17:295
  23. Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between prim...

    Authors: Antonella Manca, Panagiotis Paliogiannis, Maria Colombino, Milena Casula, Amelia Lissia, Gerardo Botti, Corrado Caracò, Paolo A. Ascierto, Maria Cristina Sini, Grazia Palomba, Marina Pisano, Valentina Doneddu, Antonio Cossu and Giuseppe Palmieri
    Citation: Journal of Translational Medicine 2019 17:289
  24. Recently the 8th version of the American Joint Committee on Cancer (AJCC) classification has been introduced, and has attempted to define a more accurate and precise definition of prognosis in line with the ma...

    Authors: Paolo Antonio Ascierto, Lorenzo Borgognoni, Gerardo Botti, Michele Guida, Paolo Marchetti, Simone Mocellin, Paolo Muto, Giuseppe Palmieri, Roberto Patuzzo, Pietro Quaglino, Ignazio Stanganelli and Corrado Caracò
    Citation: Journal of Translational Medicine 2019 17:266

    The Correction to this article has been published in Journal of Translational Medicine 2019 17:315

  25. Diagnosis of melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges in mel...

    Authors: Paolo A. Ascierto, Sanjiv S. Agarwala, Gerardo Botti, Alfredo Budillon, Michael A. Davies, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Silvia Formenti, Thomas F. Gajewski, Claus Garbe, Omid Hamid, Roger S. Lo, Jason J. Luke, Oliver Michielin, Giuseppe Palmieri…
    Citation: Journal of Translational Medicine 2019 17:234
  26. Adrenocorticotrophic hormone (ACTH)-treatment rat model has been utilized as a widely accepted model of treatment-resistant depression. Metabolomic signatures represent the pathophysiological phenotype of dise...

    Authors: Jing Song, Weini Ma, Xinyi Gu, Le Zhao, Jiaye Jiang, Ying Xu, Lei Zhang, Mingmei Zhou and Li Yang
    Citation: Journal of Translational Medicine 2019 17:224
  27. Melanoma is an aggressive type of skin cancer whose aetiology remains elusive as both environmental and genetic factors can contribute to its development. Recent studies have demonstrated the existence of mult...

    Authors: Maria Santa Rocca, Clara Benna, Simone Mocellin, Carlo Riccardo Rossi, Aichi Msaki, Andrea Di Nisio, Giuseppe Opocher and Carlo Foresta
    Citation: Journal of Translational Medicine 2019 17:181
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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

  45. 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

  46. 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
  47. 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

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