The DOI matches its Crossref record; 224 of the 230 references it cites were found in a registry or an index.
Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy
Abstract
Improved understanding of the immune system and its role in cancer development and progression has led to impressive advances in the field of cancer immunotherapy over the last decade. Whilst the field is rapidly evolving and the list of drugs receiving regulatory approval for the treatment of various cancers is fast growing, the group of PD1- PDL-1 inhibitors is establishing a leading role amongst immunomodulatory agents. PD1- PDL-1 inhibitors act against pathways involved in adaptive immune suppression resulting in immune checkpoint blockade. Within the last four years two PD-1 and three PD-L1 inhibitors have been utilized in clinical practice against a variety of malignancies. Focus was initially placed on targeting cancers considered immunogenic such as melanoma, renal and lung cancers but subsequently the application expanded to include amongst others Hodgkin Lymphoma, urothelial as well as head and neck cancer. This article provides a comprehensive review of the early and late phase trials that led to the regulatory approval of all five PD1- PDL-1 inhibitors in the corresponding cancer types. It presents available data on the combinations of PD1- PDL-1 inhibitors with other therapies (immunotherapy, targeted therapy and chemotherapy), the toxicity profile of the PD1- PDL-1 inhibitors and ongoing trials testing the efficacy of these agents in cancer types beyond those that have been addressed already. Finally, current and future challenges in the application of PD-1 and PD-L1 inhibitors are discussed with emphasis on the role of predictive biomarkers.
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“The PD-1/ PD-L1 axis is hijacked by cancer cells to counteract immune activation, allowing the tumor to escape the immune response.”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Constantinidou et al., 2019
Citations
Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Research works printed but not linked: 1
- Escudier, 2017, Annals of Oncology, 28
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Xie, J., Yang, Y., Gao, Y., & He, J. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01732-y · Cited by 843
Wang, Z., Cui, C., Yao, J., Zhang, Y., Li, M., Feng, J., Yang, S., Fan, Y., Shi, J., Zhang, X., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.02.007 · Cited by 559
Application of PD-1 Blockade in Cancer Immunotherapy
Wu, X., Gu, Z., Yang, C., Chen, B., Chen, W., Weng, L., & Liu, X. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.03.006 · Cited by 541
Signal pathways of melanoma and targeted therapy
Guo, W., Wang, H., & Li, C. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00827-6 · Cited by 419
Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment
Marzagalli, M., Ebelt, N. D., & Manuel, E. R. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.002 · Cited by 358
Metadata
- Authors
- Constantinidou, A., Alifieris, C., & Trafalis, D. T.
- Affiliations
- University of Cyprus (CY)
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Trafalis, Dimitrios T.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 194
- Pages
- 84-106
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2894101188
- Cited by
- 342
- References
- 230
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 43 · 2023: 51 · 2022: 58 · 2021: 72 · 2020: 53 · 2019: 35
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PD-1 inhibitors, PD-L1 inhibitors, immune checkpoint blockade, cancer immunotherapy, melanoma, renal cell carcinoma, lung cancer, Hodgkin's disease, urothelial carcinoma, head and neck cancer, combination therapy, toxicity profile, predictive biomarkers, regulatory approval
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Humans, Immunotherapy, Neoplasms, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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