Emerging therapeutic agents for lung cancer

Abstract

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.

Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas

“…Despite recent advances in the treatment of patients with non–small cell lung cancer (NSCLC), the overall 5‐year survival rate has remained relatively steady at 18% . Approximately 50% of patients with NSCLC present with advanced stage III or IV disease . For the majority of patients who have advanced NSCLC without a targetable driver mutation, the mainstay of therapy for the past 3 decades has been combination platinum‐based cytotoxic chemotherapy .…”

“…1 Approximately 50% of patients with NSCLC present with advanced stage III or IV disease. 2,3 For the majority of patients who have advanced NSCLC without a targetable driver mutation, the mainstay of therapy for the past 3 decades has been combination platinum-based cytotoxic chemotherapy. 4,5 Immunotherapy is being used increasingly, and since 2015, the US Food and Drug Administration has approved 3 new checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) receptor for the treatment of patients with advanced NSCLC: nivolumab, pembrolizumab, and atezolizumab.…”

Clinical applications of PD-L1 bioassays for cancer immunotherapy

“…Durable responses to agents targeting programmed cell death-1 protein receptor (PD-1) and the ligand (PD-L1) have been observed in lung cancer as well as a variety of cancer types [4–10]. PD-L1 expression varies due to the dynamic tumor microenvironment [11–15].…”

Current perspectives on the crosstalk between lung cancer stem cells and cancer-associated fibroblasts

“…Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development and extensively reviewed in refs. (Dholaria et al, 2016; (Figure 3). Examples include, among others: Napabucasin (BBI608), considered a first-in-class cancer stemness inhibitor, functions by inhibiting the STAT3 pathway, and has been evaluated in NSCLC patients in combination with paclitaxel (ClinicalTrials.gov Identifier: NCT01325441).…”

“…Recently, immunotherapy-based approaches have been successfully used to treat different types of lung cancer with high cure rates (1-and 2-year survival rates of 42% and 23%, respectively for lung cancer (Keating, 2016)); however, immunotherapy is not effective in all lung cancer patients for reasons that have yet to be determined. Thus, while different targeted therapy drugs are under development and novel therapies and new treatment strategies are showing some promise (reviewed in (Dholaria et al, 2016)), survival rates in general remain extremely low. The reason for these low survival rate statistics is believed to be due, in part, to the existence of a subpopulation of stem-like cancer stem cells (CSCs) or cancer-initiating cells (CICs) within the tumor population that are responsible for the high tumorigenic, metastatic and chemoresistant capacity of this tumor.…”