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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. The diagnosis of check-point inhibitor-related pneumonitis (CIP) relies on radiological and clinical patterns which are not specific and can mimic other conditions (cancer progression, infectious diseases or i...

    Authors: Sabino Strippoli, Livia Fucci, Antonio Negri, Daniela Putignano, Marco Luigi Cisternino, Gaetano Napoli, Ruggiero Filannino, Ivana De Risi, Angela Monica Sciacovelli and Michele Guida
    Citation: Journal of Translational Medicine 2020 18:473
  2. Cardiomyopathy is a common side effect of doxorubicin (DOX) chemotherapy. Despite intensive research efforts in the field, there is still no evidence available for routine cardioprotective prophylaxis to preve...

    Authors: Mária Lódi, Viktor Bánhegyi, Beáta Bódi, Alexandra Gyöngyösi, Árpád Kovács, Anita Árokszállási, Nazha Hamdani, Miklós Fagyas, István Édes, Zoltán Csanádi, István Czuriga, Zoltán Kisvárday, István Lekli, Péter Bai, Attila Tóth, Zoltán Papp…
    Citation: Journal of Translational Medicine 2020 18:470
  3. Information regarding characteristics and risk factors of COVID-19 amongst middle-aged (40–59 years) patients without comorbidities is scarce.

    Authors: Peng Wang, Jing Sha, Mei Meng, Cuiyan Wang, Qingchun Yao, Zhongfa Zhang, Wenqing Sun, Xingguang Wang, Guoqiang Qie, Xue Bai, Keke Liu and Yufeng Chu
    Citation: Journal of Translational Medicine 2020 18:461
  4. Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-las...

    Authors: Paolo Marchetti, Andrea Botticelli, Antonio Paolo Ascierto, Giuseppe Curigliano and Diana Giannarelli
    Citation: Journal of Translational Medicine 2020 18:446
  5. Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with...

    Authors: Nicholas Gulati, Douglas Donnelly, Yingzhi Qian, Una Moran, Paul Johannet, Judy Zhong and Iman Osman
    Citation: Journal of Translational Medicine 2020 18:430
  6. Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-1...

    Authors: Jing Zhang, Yiqun Hao, Wuling Ou, Fei Ming, Gai Liang, Yu Qian, Qian Cai, Shuang Dong, Sheng Hu, Weida Wang and Shaozhong Wei
    Citation: Journal of Translational Medicine 2020 18:406
  7. Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.

    Authors: Francesco Perrone, Maria Carmela Piccirillo, Paolo Antonio Ascierto, Carlo Salvarani, Roberto Parrella, Anna Maria Marata, Patrizia Popoli, Laurenzia Ferraris, Massimiliano M. Marrocco-Trischitta, Diego Ripamonti, Francesca Binda, Paolo Bonfanti, Nicola Squillace, Francesco Castelli, Maria Lorenza Muiesan, Miriam Lichtner…
    Citation: Journal of Translational Medicine 2020 18:405

    The Correction to this article has been published in Journal of Translational Medicine 2021 19:442

  8. It is well established that thymidylate synthase inhibitors can cause cellular toxicity through uracil DNA glycosylase (UNG2)-dependent pathways. Additionally, thymidylate synthase inhibitors and HDAC inhibito...

    Authors: Meredith S. Showler and Brian P. Weiser
    Citation: Journal of Translational Medicine 2020 18:377
  9. More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in o...

    Authors: Maurice A. Canham, John D. M. Campbell and Joanne C. Mountford
    Citation: Journal of Translational Medicine 2020 18:359
  10. Severe COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associate...

    Authors: Donogh Maguire, Marylynne Woods, Conor Richards, Ross Dolan, Jesse Wilson Veitch, Wei M. J. Sim, Olivia E. H. Kemmett, David C. Milton, Sophie L. W. Randall, Ly D. Bui, Nicola Goldmann, Allan Cameron, Barry Laird, Dinesh Talwar, Ian Godber, Alan Davidson…
    Citation: Journal of Translational Medicine 2020 18:354
  11. Unresectable or metastatic vulvar cancer has relatively poor outcomes despite chemotherapy-sensitized radiation therapy and combination cytotoxic therapy. Despite the virus-associated and immunogenic nature of...

    Authors: Oladapo Yeku, Andrea L. Russo, Hang Lee and David Spriggs
    Citation: Journal of Translational Medicine 2020 18:350
  12. The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, ...

    Authors: Paolo A. Ascierto, Igor Puzanov, Sanjiv S. Agarwala, Christian Blank, Richard D. Carvajal, Sandra Demaria, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Bernard A. Fox, Thomas F. Gajewski, Claus Garbe, Patrick Hwu, Roger S. Lo, Georgina V. Long, Jason J. Luke…
    Citation: Journal of Translational Medicine 2020 18:346
  13. 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
  14. In the rapidly evolving coronavirus disease 2019 (COVID-19) outbreak, inherent literature has been increasing at an impressive rate. Such a dynamic scenario imposes the necessity to define a new framework for ...

    Authors: Maddalena Barba, Eriseld Krasniqi, Gennaro Ciliberto and Patrizia Vici
    Citation: Journal of Translational Medicine 2020 18:315
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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

  23. 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

  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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

  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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
  45. 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
  46. 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
  47. 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

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