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  1. Article ; Online: Response to: Bintrafusp Alfa in Second-Line Treatment of Patients With NSCLC.

    Paz-Ares, Luis

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2021  Volume 16, Issue 4, Page(s) e24

    MeSH term(s) B7-H1 Antigen ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Humans ; Immunologic Factors ; Lung Neoplasms/drug therapy ; Transforming Growth Factor beta
    Chemical Substances B7-H1 Antigen ; Immunologic Factors ; Transforming Growth Factor beta
    Language English
    Publishing date 2021-02-03
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2021.01.1608
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    Zs.A 6664: Show issues Location:
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  2. Article ; Online: Extensive-Stage Small-Cell Lung Cancer: First-Line and Second-Line Treatment Options.

    Zugazagoitia, Jon / Paz-Ares, Luis

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2022  Volume 40, Issue 6, Page(s) 671–680

    Abstract: Extensive-stage small-cell lung cancer is a therapeutically challenging disease. After more than two decades without clinical progress, the addition of programmed cell death protein 1 axis blockade to platinum-based chemotherapy has demonstrated ... ...

    Abstract Extensive-stage small-cell lung cancer is a therapeutically challenging disease. After more than two decades without clinical progress, the addition of programmed cell death protein 1 axis blockade to platinum-based chemotherapy has demonstrated sustained overall survival benefit and represents the current standard of care in the first-line setting. Despite this benefit, resistance emerges relatively rapidly in virtually all patients. Although newer treatments are being incorporated in the relapse setting, marked therapeutic resistance is typically observed in patients with relapsed small-cell lung cancer (SCLC), underscoring the need of developing more effective therapies in this setting. Notably, recent progress in the understanding of the molecular biology of SCLC might bring possibilities toward molecularly informed therapeutic strategies for patients with SCLC, which could have a significant impact for improving outcomes in this disease. Here, we review current treatment options and recent progress made in the first-line and relapsed SCLC, including the role of biomarkers and new evolving therapeutic strategies.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Immune Checkpoint Inhibitors/therapeutic use ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Molecular Targeted Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Small Cell Lung Carcinoma/mortality ; Small Cell Lung Carcinoma/pathology ; Small Cell Lung Carcinoma/therapy ; Treatment Outcome
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2022-01-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.21.01881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Response to the Letter to the Editor Titled "First-Line Nivolumab Plus Ipilimumab With Chemotherapy for Metastatic NSCLC: The Updated Outcomes From CheckMate 9LA".

    Paz-Ares, Luis G / Carbone, David P

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2023  Volume 18, Issue 9, Page(s) e102–e103

    MeSH term(s) Humans ; Ipilimumab/therapeutic use ; Nivolumab/therapeutic use ; Lung Neoplasms/drug therapy ; Carcinoma, Non-Small-Cell Lung/drug therapy
    Chemical Substances Ipilimumab ; Nivolumab (31YO63LBSN)
    Language English
    Publishing date 2023-08-19
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2023.05.022
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  4. Article ; Online: Foreword to 'The current status and future perspectives on the management of stage III NSCLC: a focus on unresectable cancer treatment paradigms'.

    Paz-Ares, Luis

    British journal of cancer

    2020  Volume 123, Issue Suppl 1, Page(s) 1–2

    MeSH term(s) Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/epidemiology ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Combined Modality Therapy ; Humans ; Neoplasm Staging ; Treatment Outcome
    Language English
    Publishing date 2020-12-03
    Publishing country England
    Document type Editorial
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-020-01068-0
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  5. Article ; Online: Summary of 'The current status and future perspectives on the management of stage III NSCLC: a focus on unresectable cancer treatment paradigms'.

    Paz-Ares, Luis

    British journal of cancer

    2020  Volume 123, Issue Suppl 1, Page(s) 36

    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/radiotherapy ; Carcinoma, Non-Small-Cell Lung/surgery ; Combined Modality Therapy ; Disease Management ; Humans ; Neoplasm Staging ; Treatment Outcome
    Language English
    Publishing date 2020-12-03
    Publishing country England
    Document type Editorial
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-020-01073-3
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  6. Article ; Online: Facts and hopes on cancer immunotherapy for small cell lung cancer.

    Zugazagoitia, Jon / Osma, Handerson / Baena, Javier / Ucero, Álvaro C / Paz-Ares, Luis

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2024  

    Abstract: Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the ... ...

    Abstract Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be prominently altered in human SCLC, including, among others, T cell exclusion, downregulation of components of the MHC-class I antigen processing and presentation machinery, or upregulation of macrophage inhibitory checkpoints. New immunotherapies aiming to target some of these dominant immune suppressive features are being intensively evaluated preclinically and clinically in SCLC. They include strategies to enhance the efficacy and/or reverse features that promote intrinsic resistance to PD-1 axis inhibition (e.g., restoring MHC-class I deficiency, targeting DNA damage response [DDR]), and novel immunomodulatory agents beyond T cell checkpoint blockers (e.g., T cell redirecting strategies, antibody drug conjugates [ADCs], or macrophage checkpoint blockers). Among them, DLL3-targeted bi-specific T-cell engagers (BiTEs) are the ones that have shown the most compelling preliminary evidence of clinical efficacy, and hold promise as therapies that might contribute to further improve patient outcomes in this disease. Here, we first provide a brief overview of key tumor microenvironment features of human SCLC. Then, we update the current clinical evidence with immune checkpoint blockade and review other emerging immunotherapy strategies that are gaining increasing attention in SCLC. We finally summarize our future perspective on immunotherapy and precision oncology for this disease.
    Language English
    Publishing date 2024-04-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-1159
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    Zs.A 4223: Show issues Location:
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  7. Article ; Online: At the crossroads of immunotherapy for oncogene-addicted subsets of NSCLC.

    Otano, Itziar / Ucero, Alvaro C / Zugazagoitia, Jon / Paz-Ares, Luis

    Nature reviews. Clinical oncology

    2023  Volume 20, Issue 3, Page(s) 143–159

    Abstract: Non-small-cell lung cancer (NSCLC) has become a paradigm of precision medicine, with the discovery of numerous disease subtypes defined by specific oncogenic driver mutations leading to the development of a range of molecularly targeted therapies. Over ... ...

    Abstract Non-small-cell lung cancer (NSCLC) has become a paradigm of precision medicine, with the discovery of numerous disease subtypes defined by specific oncogenic driver mutations leading to the development of a range of molecularly targeted therapies. Over the past decade, rapid progress has also been made in the development of immune-checkpoint inhibitors (ICIs), especially antagonistic antibodies targeting the PD-L1-PD-1 axis, for the treatment of NSCLC. Although many of the major oncogenic drivers of NSCLC are associated with intrinsic resistance to ICIs, patients with certain oncogene-driven subtypes of the disease that are highly responsive to specific targeted therapies might also derive benefit from immunotherapy. However, the development of effective immunotherapy approaches for oncogene-addicted NSCLC has been challenged by a lack of predictive biomarkers for patient selection and limited knowledge of how ICIs and oncogene-directed targeted therapies should be combined. Therefore, whether ICIs alone or with chemotherapy or even in combination with molecularly targeted agents would offer comparable benefit in the context of selected oncogenic driver alterations to that observed in the general unselected NSCLC population remains an open question. In this Review, we discuss the effects of oncogenic driver mutations on the efficacy of ICIs and the immune tumour microenvironment as well as the potential vulnerabilities that could be exploited to overcome the challenges of immunotherapy for oncogene-addicted NSCLC.
    MeSH term(s) Humans ; Antineoplastic Agents/therapeutic use ; B7-H1 Antigen ; Carcinoma, Non-Small-Cell Lung/genetics ; Immunotherapy ; Lung Neoplasms/drug therapy ; Oncogenes ; Oncogene Addiction
    Chemical Substances Antineoplastic Agents ; B7-H1 Antigen
    Language English
    Publishing date 2023-01-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2491410-1
    ISSN 1759-4782 ; 1759-4774
    ISSN (online) 1759-4782
    ISSN 1759-4774
    DOI 10.1038/s41571-022-00718-x
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    Zs.A 6029: Show issues Location:
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  8. Article: Adoptive tumor infiltrating lymphocyte transfer as personalized immunotherapy.

    Diaz-Cano, Ines / Paz-Ares, Luis / Otano, Itziar

    International review of cell and molecular biology

    2022  Volume 370, Page(s) 163–192

    Abstract: Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, a large group of patients fail to respond to therapy or progress after initial response, which brings the need for additional treatment options. ... ...

    Abstract Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, a large group of patients fail to respond to therapy or progress after initial response, which brings the need for additional treatment options. Manipulating the immune system using a variety of approaches has been explored for the past years with successful results. Sustained progress has been made to understand the T cell-mediated anti-tumor responses counteracting the tumorigenesis process. The T-lymphocyte pool, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in defeating cancer. The adoptive cell transfer of autologous tumor-infiltrating lymphocytes has been used in humans for over 30 years to treat metastatic melanoma. In this review, we provide a brief history of ACT-TIL and discuss the current state of ACT-TIL clinical development in solid tumors. We also discuss how key advances in understanding genetic intratumor heterogeneity, to accurately identify neoantigens, and new strategies designed to overcome T-cell exhaustion and tumor immunosuppression have improved the efficacy of the TIL-therapy infusion. Characteristics of the TIL products will be discussed, as well as new strategies, including the selective expansion of specific fractions from the cell product or the genetic manipulation of T cells for improving the in-vivo survival and functionality. In summary, this review outlines the potential of ACT-TIL as a personalized approach for epithelial tumors and continued discoveries are making it increasingly more effective against other types of cancers.
    MeSH term(s) Adoptive Transfer/methods ; Humans ; Immunotherapy ; Immunotherapy, Adoptive/methods ; Lymphocytes, Tumor-Infiltrating/metabolism ; Lymphocytes, Tumor-Infiltrating/pathology ; Melanoma/genetics ; Melanoma/pathology
    Language English
    Publishing date 2022-05-23
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2022.04.003
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  9. Article ; Online: Emerging Strategies for the Treatment of Small Cell Lung Cancer: A Review.

    Petty, W Jeffrey / Paz-Ares, Luis

    JAMA oncology

    2022  Volume 9, Issue 3, Page(s) 419–429

    Abstract: Importance: Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long- ...

    Abstract Importance: Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking.
    Observations: This review examines the biologic characteristics of SCLC, the current treatment landscape, and ongoing efforts to identify novel therapeutic targets. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Recently, immunotherapy-based regimens have become available for the management of SCLC, with 2 programmed cell death 1 ligand 1 inhibitors approved in combination with chemotherapy for first-line treatment of extensive-stage disease. For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC. Furthermore, a wide variety of therapies and innovative combination regimens are being continuously evaluated. Potential therapeutic strategies, including aurora kinase A inhibitors, polyadenosine diphosphate-ribose polymerase inhibitors, ataxia telangiectasia and Rad3-related inhibitors, cyclin-dependent kinase 7 inhibitors, delta-like protein 3 agents, antiganglioside agents, CD47 inhibitors, and lysine-specific histone demethylase 1a inhibitors, are also being examined.
    Conclusions and relevance: Therapeutic optimization of SCLC remains a challenge, but recent trial results and drug approvals are encouraging. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC.
    MeSH term(s) Humans ; Small Cell Lung Carcinoma/drug therapy ; Small Cell Lung Carcinoma/pathology ; Lung Neoplasms/pathology ; Neoplasm Recurrence, Local ; Immunotherapy/methods ; Biological Products/therapeutic use ; Tumor Microenvironment
    Chemical Substances Biological Products
    Language English
    Publishing date 2022-12-15
    Publishing country United States
    Document type Review ; Journal Article
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2022.5631
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  10. Article ; Online: Correction: Targeting KRASG12C in Non-Small-Cell Lung Cancer: Current Standards and Developments.

    Torres-Jiménez, Javier / Espinar, Javier Baena / de Cabo, Helena Bote / Berjaga, María Zurera / Esteban-Villarrubia, Jorge / Fraile, Jon Zugazagoitia / Paz-Ares, Luis

    Drugs

    2024  

    Language English
    Publishing date 2024-05-13
    Publishing country New Zealand
    Document type Published Erratum
    ZDB-ID 120316-2
    ISSN 1179-1950 ; 0012-6667
    ISSN (online) 1179-1950
    ISSN 0012-6667
    DOI 10.1007/s40265-024-02044-1
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