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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. Concurrent chemoradiotherapy (CCRT) is a crucial treatment for non-small cell lung carcinoma (NSCLC). However, the use of deep learning (DL) models for predicting the response to CCRT in NSCLC remains unexplor...

    Authors: Jie Peng, Xudong Zhang, Yong Hu, Tianchu He, Jun Huang, Mingdan Zhao and Jimei Meng
    Citation: Journal of Translational Medicine 2024 22:896
  2. The advent of polyadenosine diphosphate ribose polymerase inhibitors (PARPi) has brought about significant changes in the field of ovarian cancer treatment. However, in 2022, Rucaparib, Olaparib, and Niraparib...

    Authors: Fen Xiao, ZhiBin Wang, Liu Qiao, Xiu Zhang, NaYiYuan Wu, Jing Wang and Xing Yu
    Citation: Journal of Translational Medicine 2024 22:778
  3. Although immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment, only a minority of colorectal cancer (CRC) patients respond to them. Enhancing tumor immunogenicity by increa...

    Authors: Haiyan Dong, Chuangyu Wen, Lu He, Jingdan Zhang, Nanlin Xiang, Liumei Liang, Limei Hu, Weiqian Li, Jiaqi Liu, Mengchen Shi, Yijia Hu, Siyu Chen, Huanliang Liu and Xiangling Yang
    Citation: Journal of Translational Medicine 2024 22:769
  4. Delta-like ligand 3 (DLL3) is highly expressed on the cell surface of small cell lung cancer (SCLC), one of the most lethal malignancies, but minimally or not in normal tissues, making it an attractive target ...

    Authors: Shengchao Lin, Yu Zhang, Jun Yao, Junjie Yang, Yang Qiu, Zhongyuan Zhu and Haiqing Hua
    Citation: Journal of Translational Medicine 2024 22:766
  5. While melanomas commonly harbor losses of 9p21, on which CDKN2A resides, the presence of additional tumor suppressor elements at this locus is incompletely characterized. Here we assess the expression levels and ...

    Authors: Vladimir Bezrookove, Imran Khan, Anukana Bhattacharjee, Juifang Fan, Robyn Jones, Anima Sharma, Mehdi Nosrati, Pierre-Yves Desprez, Nathan Salomonis, Yihui Shi, Altaf Dar and Mohammed Kashani-Sabet
    Citation: Journal of Translational Medicine 2024 22:758
  6. LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis ...

    Authors: Da Kang, Shanshan Huang, Yijun Liao, Siyuan Mi, Jingying Zhou, Yu Feng, Riming Huang, Zhen-hai Lu, Z. Z. Pan, Wenjuan Ma, Gong Chen, Jia-Xing Yue, Jingxiu Huang and R. X. Zhang
    Citation: Journal of Translational Medicine 2024 22:742
  7. With poor prognosis and high mortality, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Standard of care therapies for PDAC have included gemcitabine for the past three decades,...

    Authors: Mariam M. Konaté, Julia Krushkal, Ming-Chung Li, Li Chen, Yuri Kotliarov, Alida Palmisano, Rini Pauly, Qian Xie, P. Mickey Williams, Lisa M. McShane and Yingdong Zhao
    Citation: Journal of Translational Medicine 2024 22:733
  8. Compared to other malignancies, few studies have investigated the role of family history of cancer (FHC) in patients with lung cancer, yielding largely heterogeneous results. We performed a systematic literatu...

    Authors: Fabrizio Citarella, Kazuki Takada, Priscilla Cascetta, Pierfilippo Crucitti, Roberta Petti, Bruno Vincenzi, Giuseppe Tonini, Francesco M. Venanzi, Alessandra Bulotta, Sara Oresti, Carlo Greco, Sara Ramella, Lucio Crinò, Angelo Delmonte, Roberto Ferrara, Massimo Di Maio…
    Citation: Journal of Translational Medicine 2024 22:714
  9. Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We co...

    Authors: Li-Jun Wei, Jia Fu, Hai-Xia Yang, Xia Yang, Hao-Yu Liang, Rong-Zhen Luo and Li-Li Liu
    Citation: Journal of Translational Medicine 2024 22:655
  10. In the era of second-generation ALK tyrosine kinase inhibitors (ALK-TKIs), there was a paucity of data regarding the progression patterns, resistant mechanisms, and subsequent therapeutic approaches for ALK-po...

    Authors: Lige Wu, Zihua Zou, Yan Li, Xuezhi Hao, Jianming Ying, Junling Li and Puyuan Xing
    Citation: Journal of Translational Medicine 2024 22:585
  11. The Accum® platform was initially designed to accumulate biomedicines in target cells by inducing endosomal-to-cytosol escape. Interestingly however, the use of unconjugated Accum® was observed to trigger cell de...

    Authors: Jean Pierre Bikorimana, Nehme El-Hachem, Jamilah Abusarah, Marina Pereira Gonçalves, Roudy Farah, Gabrielle A. Mandl, Sebastien Talbot, Simon Beaudoin, Daniela Stanga, Sebastien Plouffe and Moutih Rafei
    Citation: Journal of Translational Medicine 2024 22:532
  12. Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurr...

    Authors: Riley M. Larkin, Diana C. Lopez, Yvette L. Robbins, Wiem Lassoued, Kenneth Canubas, Andrew Warner, Baktiar Karim, Ksenia Vulikh, James W. Hodge, Charalampos S. Floudas, James L. Gulley, Gary L. Gallia, Clint T. Allen and Nyall R. London Jr.
    Citation: Journal of Translational Medicine 2024 22:524

    The Correction to this article has been published in Journal of Translational Medicine 2024 22:836

  13. The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor sol...

    Authors: Nima Beheshtizadeh, Zahra Amiri, Seyedeh Zoha Tabatabaei, Amir Abbas Seraji, Maliheh Gharibshahian, Akram Nadi, Morvarid Saeinasab, Farshid Sefat and Hanieh Kolahi Azar
    Citation: Journal of Translational Medicine 2024 22:520
  14. Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' s...

    Authors: Alain Gelibter, Angela Asquino, Lidia Strigari, Ilaria Grazia Zizzari, Lucrezia Tuosto, Fabio Scirocchi, Angelica Pace, Marco Siringo, Elisa Tramontano, Serena Bianchini, Filippo Bellati, Andrea Botticelli, Donatella Paoli, Daniele Santini, Marianna Nuti, Aurelia Rughetti…
    Citation: Journal of Translational Medicine 2024 22:329
  15. The anti-apoptotic BCL-2 protein family regulates cancer cell survival, thus it represents an important therapeutic target. Indeed, a drug class, called BH3-mimetics, have been developed to directly target BCL...

    Authors: Alfredo E. Montes-Gómez and Stephen W. G. Tait
    Citation: Journal of Translational Medicine 2024 22:317
  16. Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans

    Authors: Francesca Benedetti, Emmanuel F. Mongodin, Jonathan H. Badger, Arshi Munawwar, Ashley Cellini, Weirong Yuan, Giovannino Silvestri, Carl N. Kraus, Simone Marini, Chozha V. Rathinam, Marco Salemi, Hervé Tettelin, Robert C. Gallo and Davide Zella
    Citation: Journal of Translational Medicine 2024 22:269
  17. Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The ident...

    Authors: Giulia Pasello, Aline S. C. Fabricio, Paola Del Bianco, Valentina Salizzato, Adolfo Favaretto, Luisa Piccin, Fable Zustovich, Alessio Fabozzi, Costanza De Rossi, Jacopo Pigozzo, Mattia De Nuzzo, Elia Cappelletto, Laura Bonanno, Dario Palleschi, Gian Luca De Salvo, Valentina Guarneri…
    Citation: Journal of Translational Medicine 2024 22:242
  18. Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investi...

    Authors: Shuming Chen, Tracee L. McMiller, Abha Soni, Farah Succaria, John-William Sidhom, Laura C. Cappelli, Livia A. Casciola-Rosen, Isaac R. Morales, Preethi Sankaran, Alan E. Berger, Julie Stein Deutsch, Qingfeng C. Zhu, Robert A. Anders, Jody E. Hooper, Drew M. Pardoll, Evan J. Lipson…
    Citation: Journal of Translational Medicine 2024 22:241
  19. The androgen receptor (AR) is a crucial player in various aspects of male reproduction and has been associated with the development and progression of prostate cancer (PCa). Therefore, the protein is the linch...

    Authors: Sherif Mehralivand, Christian Thomas, Martin Puhr, Frank Claessens, Arjanneke F. van de Merbel, Anna Dubrovska, Guido Jenster, Christof Bernemann, Ulrich Sommer and Holger H. H. Erb
    Citation: Journal of Translational Medicine 2024 22:71
  20. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components an...

    Authors: Antonio Agostini, Ilaria Guerriero, Geny Piro, Giuseppe Quero, Luca Roberto, Annachiara Esposito, Alessia Caggiano, Lorenzo Priori, Giulia Scaglione, Francesco De Sanctis, Antonella Sistigu, Martina Musella, Alberto Larghi, Gianenrico Rizzatti, Donatella Lucchetti, Sergio Alfieri…
    Citation: Journal of Translational Medicine 2023 21:843
  21. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the start of the pandemic, olfactory dysfunction (OD) has been rep...

    Authors: Bian Hu, Mengdan Gong, Yizhen Xiang, Siyuan Qu, Hai Zhu and Dong Ye
    Citation: Journal of Translational Medicine 2023 21:829
  22. While the efficacy of neoadjuvant chemotherapy (NACT) in treating triple-negative breast cancer (TNBC) is generally accepted, not all patients derive benefit from this preoperative treatment. Presently, there ...

    Authors: Mohamed Omar, Pier Vitale Nuzzo, Francesco Ravera, Sara Bleve, Giuseppe Nicolò Fanelli, Claudio Zanettini, Itzel Valencia and Luigi Marchionni
    Citation: Journal of Translational Medicine 2023 21:811
  23. The combination of nivolumab + relatlimab is superior to nivolumab alone in the treatment of naive patients and has activity in PD-1 refractory melanoma. We had previously observed a reduced expression of LAG3 in...

    Authors: Domenico Mallardo, Rachel Woodford, Alexander M. Menzies, Lisa Zimmer, Andrew williamson, Egle Ramelyte, Florentia Dimitriou, Alexandre Wicky, Roslyn Wallace, Mario Mallardo, Alessio Cortellini, Alfredo Budillon, Victoria Atkinson, Shahneen Sandhu, Michielin Olivier, Reinhard Dummer…
    Citation: Journal of Translational Medicine 2023 21:753
  24. Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma.

    Authors: Domenico Mallardo, Mario Fordellone, Andrew White, Margaret Ottaviano, Francesca Sparano, Michael Bailey, Arianna Bianca Facchini, Sufey Ong, Piera Maiolino, Corrado Caracò, Sarah Church, Ernesta Cavalcanti, Sarah Warren, Alfredo Budillon, Alessandra Cesano, Ester Simeone…
    Citation: Journal of Translational Medicine 2023 21:610
  25. Lung cancer is the leading cause of cancer deaths worldwide. Despite never smokers comprising between 10 and 25% of all cases, lung cancer in never smokers (LCNS) is relatively under characterized from an etio...

    Authors: Peiyao Wang, Sophie Sun, Stephen Lam and William W. Lockwood
    Citation: Journal of Translational Medicine 2023 21:585
  26. The prognosis of esophageal adenocarcinoma (EAC) and gastric adenocarcinoma (GAC) remains poor, and new therapeutic approaches are urgently needed. Claudin 6 (CLDN6) is an oncofetal antigen that is largely abs...

    Authors: Adrian Georg Simon, Su Ir Lyu, Mark Laible, Stefan Wöll, Özlem Türeci, Uğur Şahin, Hakan Alakus, Luca Fahrig, Thomas Zander, Reinhard Buettner, Christiane Josephine Bruns, Wolfgang Schroeder, Florian Gebauer and Alexander Quaas
    Citation: Journal of Translational Medicine 2023 21:552
  27. Novel therapies have achieved unprecedented benefit in survival of advanced melanoma patients. While immunotherapy (ICI) can be administered independent of mutational status, BRAF and MEK kinase inhibitors rep...

    Authors: Reinhard Dummer, Michèle Welti and Egle Ramelyte
    Citation: Journal of Translational Medicine 2023 21:529
  28. Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), pro...

    Authors: Paolo A. Ascierto, Sanjiv S. Agarwala, Allison Betof Warner, Marc S. Ernstoff, Bernard A. Fox, Thomas F. Gajewski, Jérôme Galon, Claus Garbe, Brian R. Gastman, Jeffrey E. Gershenwald, Pawel Kalinski, Michelle Krogsgaard, Rom S. Leidner, Roger S. Lo, Alexander M. Menzies, Olivier Michielin…
    Citation: Journal of Translational Medicine 2023 21:508
  29. The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover...

    Authors: Jessica Wenthe, Emma Eriksson, Ann-Charlotte Hellström, Rafael Moreno, Gustav Ullenhag, Ramon Alemany, Tanja Lövgren and Angelica Loskog
    Citation: Journal of Translational Medicine 2023 21:506
  30. Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the char...

    Authors: Xianwang Wang, Yihua Shen, Xingxia Wan, Xiaoqing Hu, Wen-Qi Cai, Zijun Wu, Qiang Xin, Xiaoqing Liu, Jingang Gui, Hong-Yi Xin and Hong-Wu Xin
    Citation: Journal of Translational Medicine 2023 21:500
  31. The discovery and development of novel treatments that harness the patient’s immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. However, not all patien...

    Authors: Paolo A. Ascierto, Antonio Avallone, Carlo Bifulco, Sergio Bracarda, Joshua D. Brody, Leisha A. Emens, Robert L. Ferris, Silvia C. Formenti, Omid Hamid, Douglas B. Johnson, Tomas Kirchhoff, Christopher A. Klebanoff, Gregory B. Lesinski, Anne Monette, Bart Neyns, Kunle Odunsi…
    Citation: Journal of Translational Medicine 2023 21:488
  32. Viral therapies developed for cancer treatment have classically prioritized direct oncolytic effects over their immune activating properties. However, recent clinical insights have challenged this longstanding...

    Authors: Josef W. Goldufsky, Preston Daniels, Michael D. Williams, Kajal Gupta, Bruce Lyday, Tony Chen, Geeta Singh, Howard L. Kaufman, Andrew Zloza and Amanda L. Marzo
    Citation: Journal of Translational Medicine 2023 21:483
  33. Immune checkpoint inhibitor therapy has revolutionized the clinical management of a diverse range of cancer types, including advanced cutaneous melanoma. While immunotherapy targeting the PD-1/PD-L1 system has...

    Authors: Yue Li, Ben Wu, Md Jakir Hossain, Lily Quagliata, Connor O’Meara, Marc R. Wilkins, Susan Corley and Levon M. Khachigian
    Citation: Journal of Translational Medicine 2023 21:467
  34. Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, app...

    Authors: Guozhen Yang, Xiaodong Su, Yuanheng Huang, Guangyu Luo, Zhiqiang Wang, Peiqiang Cai, Yating Zheng, Ting Bei, Mengli Huang, Yuezong Bai, Haoqiang He, Jin Xiang, Muyan Cai, Jiudi Zhong, Qiyu Guo and Xu Zhang
    Citation: Journal of Translational Medicine 2023 21:411
  35. To evaluate a new class of blood-based biomarkers, anti-frameshift peptide antibodies, for predicting both tumor responses and adverse immune events to immune checkpoint inhibitor (ICI) therapies in advanced l...

    Authors: Luhui Shen, Justin R. Brown, Stephen Albert Johnston, Mehmet Altan and Kathryn F. Sykes
    Citation: Journal of Translational Medicine 2023 21:338
  36. Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe off-targe...

    Authors: Domenico Galati, Serena Zanotta, Mariaelena Capone, Gabriele Madonna, Domenico Mallardo, Marilena Romanelli, Ester Simeone, Lucia Festino, Francesca Sparano, Rosa Azzaro, Rosaria De Filippi, Antonio Pinto, Chrystal M. Paulos and Paolo A. Ascierto
    Citation: Journal of Translational Medicine 2023 21:318
  37. The taxonomy of Kaposi Sarcoma (KS) is based on a classification system focused on the description of clinicopathological features of KS in geographically and clinically diverse populations. The classification...

    Authors: M. R. Openshaw, E. Gervasi, C. A. M. Fulgenzi, D. J. Pinato, A. Dalla Pria and M. Bower
    Citation: Journal of Translational Medicine 2023 21:283
  38. The 2022 Immunotherapy Bridge congress (November 30–December 1, Naples, Italy) featured a Great Debate session which addressed three contemporary topics in the field of immunotherapy. The debates included coun...

    Authors: Paolo A. Ascierto, Renier Brentjens, Samir N. Khleif, Kunle Odunsi, Katayoun Rezvani, Marco Ruella, Ryan J. Sullivan, Bernard A. Fox and Igor Puzanov
    Citation: Journal of Translational Medicine 2023 21:275
  39. The Great Debate session at the 2022 Melanoma Bridge congress (December 1–3) featured counterpoint views from leading experts on five contemporary topics of debate in the management of melanoma. The debates co...

    Authors: Paolo A. Ascierto, Christian Blank, Alexander M. Eggermont, Claus Garbe, Jeffrey E. Gershenwald, Omid Hamid, Axel Hauschild, Jason J. Luke, Janice M. Mehnert, Jeffrey A. Sosman, Hussein A. Tawbi, Mario Mandalà, Alessandro Testori, Corrado Caracò, Iman Osman and Igor Puzanov
    Citation: Journal of Translational Medicine 2023 21:265
  40. Gene expression profiling is increasingly being utilised as a diagnostic, prognostic and predictive tool for managing cancer patients. Single-sample scoring approach has been developed to alleviate instability...

    Authors: Yizhe Mao, Tuba N. Gide, Nurudeen A. Adegoke, Camelia Quek, Nigel Maher, Alison Potter, Ellis Patrick, Robyn P. M. Saw, John F. Thompson, Andrew J. Spillane, Kerwin F. Shannon, Matteo S. Carlino, Serigne N. Lo, Alexander M. Menzies, Inês Pires da Silva, Georgina V. Long…
    Citation: Journal of Translational Medicine 2023 21:257
  41. The mechanism of tumor immune escape and progression in colorectal cancer (CRC) is widely investigated in-vitro to help understand and identify agents that might play a crucial role in response to treatment and i...

    Authors: Nassiba Taib, Maysaloun Merhi, Varghese Inchakalody, Sarra Mestiri, Shereena Hydrose, Karama Makni-Maalej, Afsheen Raza, Fairooz Sahir, Fouad Azizi, Parveen B. Nizamuddin, Queenie Fernandes, Zeenath Safira K. M. Yoosuf, Salam Almoghrabi, Lobna Al-Zaidan, Alaaeldin Shablak, Shahab Uddin…
    Citation: Journal of Translational Medicine 2023 21:235
  42. Head and Neck Squamous Cell Carcinoma is a malignant tumor with high morbidity and mortality. The MMP family plays an important role in tumor invasion and metastasis. However, the mechanistic value of the MMP ...

    Authors: Maohua Liu, Lijuan Huang, Yunling Liu, Sen Yang, Yong Rao, Xiao Chen, Minhai Nie and Xuqian Liu
    Citation: Journal of Translational Medicine 2023 21:208
  43. Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. ...

    Authors: Domenico Mallardo, Ester Simeone, Lucia Festino, Marilena Tuffanelli, Vito Vanella, Claudia Trojaniello, Maria Grazia Vitale, Margaret Ottaviano, Mariaelena Capone, Gabriele Madonna, Francesca Sparano, Eleonora Cioli, Luigi Scarpato, Marco Palla, Rossella Di Trolio, Paolo Meinardi…
    Citation: Journal of Translational Medicine 2023 21:140
  44. Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few stud...

    Authors: Rong Huang, Gaigai Shen, Yu Ren, Kelin Zheng, Jiayu Wang, Yan Shi, Jiani C. Yin, Lanqun Qin, Guiying Zhang, Mengke Zhao, Xinyu Su, Luqiao Li, Fufeng Wang, Yang Shao, Baorui Liu and Zhengyun Zou
    Citation: Journal of Translational Medicine 2023 21:78
  45. Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not posto...

    Authors: Zhaoya Gao, Dandan Huang, Hui Chen, Yong Yang, Ke An, Changmin Ding, Zheping Yuan, Zhichao Zhai, Pengfei Niu, Qingkun Gao, Jinping Cai, Qingmin Zeng, Yanzhao Wang, Yuming Hong, Wanshui Rong, Wensheng Huang…
    Citation: Journal of Translational Medicine 2023 21:63

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