Emerging therapeutic agents for lung cancer

Journal of Hematology & Oncology, Dec 2016

Lung cancer continues to be the most common cause of cancer-related mortality worldwide. Recent advances in molecular diagnostics and immunotherapeutics have propelled the rapid development of novel treatment agents across all cancer subtypes, including lung cancer. Additionally, more pharmaceutical therapies for lung cancer have been approved by the US Food and Drug Administration in the last 5 years than in previous two decades. These drugs have ushered in a new era of lung cancer managements that have promising efficacy and safety and also provide treatment opportunities to patients who otherwise would have no conventional chemotherapy available. In this review, we summarize recent advances in lung cancer therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to drugs in their class or are a completely new class of drugs with novel mechanisms of action. We have divided our discussion into targeted agents, immunotherapies, and antibody drug conjugates for small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). We briefly review the emerging agents and ongoing clinical studies. We have attempted to provide the most current review on emerging therapeutic agents on horizon for lung cancer.

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Emerging therapeutic agents for lung cancer

Dholaria et al. Journal of Hematology & Oncology Emerging therapeutic agents for lung cancer Bhagirathbhai Dholaria 0 William Hammond 0 Amanda Shreders 0 Yanyan Lou 0 0 Department of Hematology-Oncology, Mayo Clinic , 4500 San Pablo Road, Jacksonville, FL 32224 , USA Lung cancer continues to be the most common cause of cancer-related mortality worldwide. Recent advances in molecular diagnostics and immunotherapeutics have propelled the rapid development of novel treatment agents across all cancer subtypes, including lung cancer. Additionally, more pharmaceutical therapies for lung cancer have been approved by the US Food and Drug Administration in the last 5 years than in previous two decades. These drugs have ushered in a new era of lung cancer managements that have promising efficacy and safety and also provide treatment opportunities to patients who otherwise would have no conventional chemotherapy available. In this review, we summarize recent advances in lung cancer therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to drugs in their class or are a completely new class of drugs with novel mechanisms of action. We have divided our discussion into targeted agents, immunotherapies, and antibody drug conjugates for small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). We briefly review the emerging agents and ongoing clinical studies. We have attempted to provide the most current review on emerging therapeutic agents on horizon for lung cancer. Lung cancer; Targeted agents; Immunotherapy; Phase I/II clinical trial - Background Lung cancer is the second most commonly diagnosed cancer and is the leading cause of cancer-related death in both men and women. Implementation of tobacco control, low-dose spiral computed tomography screening programs, and advances in multidisciplinary treatments have resulted in the slow decline of both incidence and mortality. However, 52–58% of lung cancer patients present with advanced-stage disease, and a vast majority of these patients do not survive despite treatment. Similarly, the prognosis remains poor even in locally advanced disease because of the high relapse rate and early formation of micrometastases [1]. One of the most important therapeutic advances of lung cancer treatment in the last decade was identification of specific driver mutations and the development of small molecular tyrosine kinase inhibitors (TKIs) [2]. In 2009, erlotinib was the first selective epidermal growth factor receptor (EGFR) inhibitor approved by the US Food and Drug Administration (FDA) [3]. This was quickly followed by crizotinib, which was initially developed as a MET (mesenchymal-to-epithelial transition/hepatocyte growth factor receptor) inhibitor and was found to be highly active against small subset of non-small-cell lung cancer (NSCLC) cases harboring anaplastic lymphoma kinase (ALK) rearrangement [4]. These drugs promise around a 70% response rate; however, resistance development is almost universal, and second/third generation TKIs are being developed to overcome these issues. Novel targeted agents directed against EGFR, ALK, ROS1, MET, RET, BRAF, and many more are under investigation. Figure 1 provides summary of targets with specific focus on the drugs that currently in early-phase clinical trials in lung cancer. In addition to these drugs, next-generation sequencing and cell-free DNA (cfDNA) technologies have provided rapid and convenient tools for gene abnormality testing and the development of targeted therapies [5]. Additionally, personalized medicine has become part of daily practice, and tailoring treatment for individual patients is becoming a reality. Immunotherapy in the form of checkpoint inhibitors represents a landmark success in NSCLC treatment, and © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fig. 1 Molecular targets and inhibiting agents being studied in phase I/II trials as potential therapy for patients with lung cancer. Abbreviations: AKT protein kinase B, ALK anaplastic lymphoma kinase, CREB3L2 cyclic AMP-responsive element-binding protein 3-like protein 2, EGFR epidermal growth factor receptor, EML4 echinoderm microtubule-associated protein-like 4, ERK extracellular signal-regulated kinase, FGFR fibroblast growth factor receptor, HGF hepatocyte growth factor, MCL1 myeloid leukemia cell differentiatio (...truncated)


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Bhagirathbhai Dholaria, William Hammond, Amanda Shreders, Yanyan Lou. Emerging therapeutic agents for lung cancer, Journal of Hematology & Oncology, 2016, pp. 138, 9, DOI: 10.1186/s13045-016-0365-z