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Combination Strategies

Section edited by Paolo A. Ascierto and Alessio Cortellini

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. Characteristics of patients significantly differ between registrational clinical trials (CTs) and Italian real-world practice, with older median age, higher elderly (≥ 65) rate and worse performance status (PS...

    Authors: Maria Lucia Iacovino, Simone Talucci, Laura Arenare, Andrea Caglio, Andrea Canciello, Flavio Salerno, Sergio Facchini, Adriano Gravina, Clorinda Schettino, Maria Carmela Piccirillo, Pier Paolo Olimpieri, Massimo Di Maio and Francesco Perrone
    Citation: Journal of Translational Medicine 2025 23:547
  2. Anti-androgen resistance remains a major clinical challenge in the treatment of prostate cancer (PCa), leading to disease progression and treatment failure. Despite extensive research on resistance mechanisms,...

    Authors: Ruilin Zhuang, Ruihui Xie, Shirong Peng, Qianghua Zhou, Weilong Lin, Yuan Ou, Bingliang Chen, Tong Su, Zean Li, Hai Huang, Kaiwen Li and Yu Duan
    Citation: Journal of Translational Medicine 2025 23:480
  3. Clinical trials have shown that neoadjuvant anlotinib combined with PD-1 blockade therapy can prolong the survival of patients with driver gene negative non-small cell lung cancer (NSCLC), but some patients fa...

    Authors: Ziqi Huang, Li Li, Xiaohe Zhao, Haixia Jin, Meng Shen, Baihui Li, Yu Zeng, Qinfen Zhang, Qiyu Wang, Meng Wang and Lili Yang
    Citation: Journal of Translational Medicine 2025 23:478
  4. Integration of immune checkpoint inhibitors (ICIs) with non-immune therapies relies on identifying combinatorial biomarkers, which are essential for patient stratification and personalized treatment.

    Authors: Jiaxin Wen, Yanfeng Wang, Song Wang, Yuxin Liang, Xiaozhen Hu, Qiuxiang Ou, Hua Bao, Kuo Zhao and Youyu Wang
    Citation: Journal of Translational Medicine 2025 23:467
  5. Immunogenic cell death (ICD) is a distinct subtype of regulatory cell death, and represents a potential mechanism to remodel the tumor microenvironment. Lenvatinib is established as the first-line therapy for ...

    Authors: Yingzheng Tan, Lei Yang, Tao Xu, Qingbin Wang, Meiyuan Huang, Zhijian Zhao, Xun Chen, Caixi Tang and Wenliang Tan
    Citation: Journal of Translational Medicine 2025 23:456
  6. Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a central role in the immune system, orchestrating immune response against tumors. We previously demonstrated that DC-based vaccin...

    Authors: Jenny Bulgarelli, Claudia Piccinini, Emanuela Scarpi, Giorgia Gentili, Laura Renzi, Silvia Carloni, Francesco Limarzi, Elena Pancisi, Anna Maria Granato, Massimiliano Petrini, Francesco De Rosa, Massimo Guidoboni, Dalila Fanelli, Maria Maddalena Tumedei, Marcella Tazzari, Stefano Baravelli…
    Citation: Journal of Translational Medicine 2025 23:455
  7. Many cases of advanced hepatocellular carcinoma (HCC) are resistant to the widely used drug sorafenib, which worsens prognosis. While many studies have explored how acquired resistance emerges during drug expo...

    Authors: Menghui Wang, Yueheng Li, Junhui Su, Xinjue Dong, Ao Liu, Yuqi Yang, Xinyi Tang, Ruijie Chen, QingQuan Li, Hongshan Wang and Hong Xiao
    Citation: Journal of Translational Medicine 2025 23:435
  8. LGALS3BP, also referred as Gal-3BP, Mac2-BP, or 90 K, is a heavily glycosylated, secreted protein prominently localized at the surface of cancer-derived extracellular vesicles (EVs). Its levels are significant...

    Authors: Ilaria Cela, Emily Capone, Asia Pece, Giulio Lovato, Pasquale Simeone, Martina Colasante, Alessia Lamolinara, Anna Piro, Manuela Iezzi, Paola Lanuti, Vincenzo De Laurenzi, Rodolfo Ippoliti, Stefano Iacobelli and Gianluca Sala
    Citation: Journal of Translational Medicine 2025 23:431
  9. Metastatic breast cancer (BC) is the main cause of cancer-related mortality in women worldwide. HR + /HER2- BC patients are treated with endocrine therapy (ET), but therapeutic resistance is common. The combin...

    Authors: Miriam González-Conde, Celso Yáñez, Carmen Abuín, Corinna Keup, Ramón Lago-Lestón, Maribel Aybar, Lucía Pedrouzo, Patricia Palacios, Teresa Curiel, Juan Cueva, Carmela Rodríguez, Marta Carmona, Alexandra Cortegoso, Tomás García-Caballero, Laura Muinelo-Romay, Sabine Kasimir-Bauer…
    Citation: Journal of Translational Medicine 2025 23:400
  10. Recent advancements in cancer therapies have improved clinical outcomes, yet therapeutic resistance remains a significant challenge because of its complex mechanisms. Among epigenetic factors, m5C RNA modifica...

    Authors: Fang Li, Tingting Liu, Yajing Dong, Qianqian Gao, Rongzhu Lu and Zhiyong Deng
    Citation: Journal of Translational Medicine 2025 23:390
  11. Studies have shown that in the pathogenesis of head and neck squamous cell carcinoma, immune circulation obstruction caused by various factors including metabolic abnormalities, gene mutations, and matrix barr...

    Authors: Yangjian Hong, Yanyang Liu, Huize Shen, Bowen Li and Qinglin Li
    Citation: Journal of Translational Medicine 2025 23:354
  12. Neoadjuvant chemoimmunotherapy (NACI) has emerged as the standard treatment for early-stage triple-negative breast cancer (TNBC). However, reliable biomarkers for identifying patients who are likely to benefit...

    Authors: Yilin Chen, Yuhong Huang, Wei Li, Teng Zhu, Minyi Cheng, Cangui Wu, Liulu Zhang, Hao Peng and Kun Wang
    Citation: Journal of Translational Medicine 2025 23:352
  13. Prostate cancer (PCa) is a leading cause of cancer-related mortality in men globally. While androgen deprivation therapy (ADT) can extend the asymptomatic phase and overall survival of patients with metastatic...

    Authors: Yuqi Guo, Zhiyuan Zhang, Lintao Dong, Xinyi Shi, Xiaohan Li, Mingxiu Luo, Yajuan Fu and Yujing Gao
    Citation: Journal of Translational Medicine 2025 23:347
  14. RC48 is an antibody-drug conjugate (ADC) specifically targeting HER2. Phase II and III clinical trials have proven its significant anti-tumor effect against locally advanced or metastatic urothelial carcinoma ...

    Authors: Huaixi Ge, Changxue Liu, Chengquan Shen, Ding Hu, Xinzhao Zhao, Yanhua Wang, Huimin Ge, Ruize Qin, Xiaocheng Ma and Yonghua Wang
    Citation: Journal of Translational Medicine 2025 23:243
  15. Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial malignancy. It is characterized by insufficient infiltration of anti-tumor T lymphocytes within the tumor microenvironment (...

    Authors: Guochen Li, Haiyan Yang, Tengfei Ke, Na Tan, Xiaolan Du, Xirui Duan, Xinyan Zhou, Guangrong Zheng and Chengde Liao
    Citation: Journal of Translational Medicine 2025 23:164
  16. Transarterial chemoembolization (TACE) is the first-line therapeutic option for patients with intermediate-stage hepatocellular carcinoma (HCC). Tumor neovascularization allows tumor growth and may facilitate ...

    Authors: María L. Espejo-Cruz, Sandra González-Rubio, Juan J. Espejo, Javier M. Zamora-Olaya, María Prieto-Torre, Clara I. Linares, Álvaro Ruiz-Ramas, Álvaro Jiménez-Arranz, Marta Guerrero-Misas, Pilar Barrera-Baena, Antonio Poyato-González, José L. Montero, Marina Sánchez-Frías, María D. Ayllón, Manuel L. Rodríguez-Perálvarez, Manuel de la Mata…
    Citation: Journal of Translational Medicine 2025 23:139
  17. HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance and incomplete r...

    Authors: Laura Scalambra, Francesca Ruzzi, Olga Maria Pittino, Maria Sofia Semprini, Chiara Cappello, Stefania Angelicola, Arianna Palladini, Patrizia Nanni, Louise Goksøyr, Cyrielle Fougeroux, Manuel L. Penichet, Adam Frederik Sander and Pier-Luigi Lollini
    Citation: Journal of Translational Medicine 2025 23:136
  18. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors play a pivotal role in treating various tumors; however, the clinical characteristics and molecular mechanisms of their associated...

    Authors: Shengkun Peng, MinHong Cai, Hongyu Kuang, Anqi Lin, Qinghua Ma, Xiaoqin Dai, Peng Luo, Yijun Liu, Guo Zhang and Yifeng Bai
    Citation: Journal of Translational Medicine 2025 23:109
  19. Although the TNM staging system plays a critical role in guiding adjuvant chemotherapy for colorectal cancer (CRC), its precision for risk stratification in stage II and III CRC patients with proficient DNA mi...

    Authors: Tong Wu, Lin Fang, Yuli Ruan, Mengde Shi, Dan Su, Yue Ma, Ming Ma, Bojun Wang, Yuanyu Liao, Shuling Han, Xiaolin Lu, Chunhui Zhang, Chao Liu and Yanqiao Zhang
    Citation: Journal of Translational Medicine 2025 23:107
  20. KRAS-G12C inhibitors mark a notable advancement in targeted cancer therapies, yet identifying predictive biomarkers for treatment efficacy and resistance remains essential for optimizing clinical outcomes.

    Authors: Linyan Tian, Chengming Liu, Sufei Zheng, Huiyang Shi, Fang Wei, Wenxin Jiang, Yucheng Dong, Haiyan Xu, Enzhi Yin, Nan Sun, Jie He and Yan Wang
    Citation: Journal of Translational Medicine 2025 23:82
  21. Almonertinib is the initial third-generation EGFR-TKI in China, but its resistance mechanism is unknown. Cancer-associated fibroblasts (CAFs) are essential matrix components in the tumor microenvironment, but ...

    Authors: Guohao Wei, Yu Nie, Min Sun, Wenzheng Zhou, Huihui Zhao, Fangfang Chen and Chuandong Zhu
    Citation: Journal of Translational Medicine 2025 23:42
  22. A novel anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center p...

    Authors: Chenfei Zhou, Bin Wang, Christina Teng, Hui Yang, Sarina A. Piha-Paul, Gary Richardson, Ashanya Malalasekera, Yajun Sun, Wei Wang, Jieqiong Liu, Yan Shi, Xianbao Zhan and Charlotte Lemech
    Citation: Journal of Translational Medicine 2025 23:37
  23. Recent studies have highlighted the distinct ratio of PD-1 + Treg/PD-1 + CD8 for prognosis prediction. However, it remains unclear about the association of this ratio and tertiary lymphoid structures (TLS) wit...

    Authors: Xu Liu, Danhua Xu, Chengbei Zhou, Yiqing Zhong, Haigang Geng, Chen Huang, Yanying Shen, Xiang Xia, Chaojie Wang, Chunchao Zhu and Hui Cao
    Citation: Journal of Translational Medicine 2024 22:1152
  24. Bortezomib is a standard treatment for multiple myeloma (MM), working by the accumulation of toxic misfolded proteins in cancer cells. However, a significant clinical challenge arises from the development of r...

    Authors: Chang-Tze Ricky Yu, Yu-Ting Amber Liao, Chi-Yin Nina Chiang, Jo-Mei Maureen Chen, Hsin-Yu Bella Pan, Chia-Yun Pan, Wei-Jun Jiang, Jia-Rung Tsai, Tsung-Ying Yang and Chieh-Lin Jerry Teng
    Citation: Journal of Translational Medicine 2024 22:1095
  25. The introduction of adjuvant therapies for patients with resected cutaneous melanoma (CM) has increased the need for sensitive biomarkers for risk stratification and disease monitoring. This study aims to inve...

    Authors: Sara Marchisio, Alessia Andrea Ricci, Gabriele Roccuzzo, Eleonora Bongiovanni, Erika Ortolan, Luca Bertero, Enrico Berrino, Valentina Pala, Renata Ponti, Paolo Fava, Simona Osella-Abate, Silvia Deaglio, Caterina Marchiò, Anna Sapino, Rebecca Senetta, Ada Funaro…
    Citation: Journal of Translational Medicine 2024 22:1074
  26. The introduction of antibody–drug conjugates represents a significant advancement in targeted therapy of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Our study aims to investigate the r...

    Authors: Andrea Ghelli Luserna di Rorà, Mouna Jandoubi, Antonella Padella, Anna Ferrari, Andrea Marranci, Cristina Mazzotti, Francesco Olimpico, Martina Ghetti, Lorenzo Ledda, Maria Teresa Bochicchio, Matteo Paganelli, Michele Zanoni, Alessandro Cafaro, Chiara Servili, Sara Galimberti, Michele Gottardi…
    Citation: Journal of Translational Medicine 2024 22:1062
  27. Currently, there is a lack of biomarkers to identify breast cancer (BC) patients who would benefit from CDK4/6 inhibitors. This study combined machine learning (ML) algorithms based on transcriptomic data with...

    Authors: Zhidong Huang, Kaixin Lou, Mengyang Qi, Jinhui Wang, Linwei Li, Bo Sun, Chen Wang, Xirui Zhou, Debo Chen and Hong Liu
    Citation: Journal of Translational Medicine 2024 22:1052
  28. Interleukin-18, a member of the interleukin − 1 family of cytokines, is upregulated in glioma. However, its effects on glioma remain unclear. This study aimed to explore the role and underlying mechanisms of i...

    Authors: Huangyi Ji, Yufei Lan, Pengpeng Xing, Zhao Wang, Xiangyang Zhong, Wenhui Tang, Quantang Wei, Hongbin Chen, Boyang Liu and Hongbo Guo
    Citation: Journal of Translational Medicine 2024 22:951
  29. Chimeric antigen receptor (CAR)-NK cell therapy has shown remarkable clinical efficacy and safety in the treatment of hematological malignancies. However, this efficacy was limited in solid tumors owing to hos...

    Authors: Xiaotong Lin, Zishen Liu, Xin Dong, Kunyuan Wang, Yao Sun, Han Zhang, Fei Wang, Ying Chen, Jing Ling, Yuetong Guo, Hongjin Xiang, Qiankun Xie, Yuqin Zhang, Zhaoze Guo, Ryohichi Sugimura and Guozhu Xie
    Citation: Journal of Translational Medicine 2024 22:929
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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

  42. 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
  43. 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
  44. 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
  45. 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

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