Abstract
Advances in the interpretation and understanding of cancer behaviour, particularly of its ability to evade the host immunosurveillance, deregulating the balance between inhibitory and stimulatory factors, led to the development of an innovative category of immunotherapeutic agents, currently under investigation. Although the disappointing data deriving from the employment of vaccines in non-small cell lung cancer (NSCLC), more promising results have been obtained in the early phase trials with immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This review delineates the main features of the available immunotherapeutic agents, focusing the discussion on immune checkpoint inhibitors, those that have already demonstrated a relevant clinical activity (such as Ipilimumab and Nivolumab) and those molecules still in early development phase. Moreover, we underline the possible emerging issues deriving from the progressive diffusion of Immuno-Oncology into the standard clinical practice. The careful and accurate identification and management of immune-related toxicities, the validation of more reliable immune response criteria and the increasing research of potential predictive biomarkers are key points of discussion. The perspective is that immunotherapy might represent an effective ‘magic bullet’, able to change the treatment paradigm of NSCLC, particularly of those subgroups featured by a heavily mutant cancer (squamous histology and smokers), where the immunologic agents contribute in cancer development and progression seems to be strong and, concurrently, the efficacy of standard therapies particularly limited.
Keywords: Checkpoint inhibitors, CTLA-4, immunotherapy, Ipilimumab, Nivolumab, Non-small cell lung cancer, PD-1.
Anti-Cancer Agents in Medicinal Chemistry
Title:Immune Checkpoint Inhibitors for Non-small-cell Lung Cancer: Does that Represent a ‘New Frontier’?
Volume: 15 Issue: 3
Author(s): Sara Pilotto, Stefania Kinspergher, Umberto Peretti, Anna Calio, Luisa Carbognin, Roberto Ferrara, Matteo Brunelli, Marco Chilosi, Giampaolo Tortora and Emilio Bria
Affiliation:
Keywords: Checkpoint inhibitors, CTLA-4, immunotherapy, Ipilimumab, Nivolumab, Non-small cell lung cancer, PD-1.
Abstract: Advances in the interpretation and understanding of cancer behaviour, particularly of its ability to evade the host immunosurveillance, deregulating the balance between inhibitory and stimulatory factors, led to the development of an innovative category of immunotherapeutic agents, currently under investigation. Although the disappointing data deriving from the employment of vaccines in non-small cell lung cancer (NSCLC), more promising results have been obtained in the early phase trials with immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This review delineates the main features of the available immunotherapeutic agents, focusing the discussion on immune checkpoint inhibitors, those that have already demonstrated a relevant clinical activity (such as Ipilimumab and Nivolumab) and those molecules still in early development phase. Moreover, we underline the possible emerging issues deriving from the progressive diffusion of Immuno-Oncology into the standard clinical practice. The careful and accurate identification and management of immune-related toxicities, the validation of more reliable immune response criteria and the increasing research of potential predictive biomarkers are key points of discussion. The perspective is that immunotherapy might represent an effective ‘magic bullet’, able to change the treatment paradigm of NSCLC, particularly of those subgroups featured by a heavily mutant cancer (squamous histology and smokers), where the immunologic agents contribute in cancer development and progression seems to be strong and, concurrently, the efficacy of standard therapies particularly limited.
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Pilotto Sara, Kinspergher Stefania, Peretti Umberto, Calio Anna, Carbognin Luisa, Ferrara Roberto, Brunelli Matteo, Chilosi Marco, Tortora Giampaolo and Bria Emilio, Immune Checkpoint Inhibitors for Non-small-cell Lung Cancer: Does that Represent a ‘New Frontier’?, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (3) . https://dx.doi.org/10.2174/1871520614666141110170259
DOI https://dx.doi.org/10.2174/1871520614666141110170259 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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