Personalizing NSCLC therapy by characterizing tumors using TKI-PET and immuno-PET

Abstract

Non-small cell lung cancer (NSCLC) therapy has entered a rapidly advancing era of precision medicine with an ever increasing number of drugs directed against a variety of specific tumor targets. Amongst these new agents, tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) are most frequently used. However, as only a sensitive subgroup of patients benefits from targeting drugs, predictive biomarkers are needed. Positron emission tomography (PET) may offer such a biomarker for predicting therapy efficacy. Some of the TKIs and mAbs that are in clinical use can be radioactively labeled and used as tracers. PET can visualize and quantify tumor specific uptake of radiolabeled targeting drugs, allowing for characterization of their pharmacokinetic behavior. In this review, the clinical potential of PET using radiolabeled TKIs (TKI-PET) and mAbs (immuno-PET) in NSCLC is discussed, and an overview is provided of the most relevant preclinical and clinical studies.

Efficacy of a small molecule inhibitor of the transcriptional cofactor PC4 in prevention and treatment of non-small cell lung cancer

“…Indicated modalities for NSCLC, including tyrosine kinase inhibitors and monoclonal antibodies that target either EGFR, ALK or PD1, have been demonstrated to improve clinical outcome in target-positive tumors. In patients with target-negative tumors, however, most of these drugs have showed very limited impact [2]. In the present study, we have shown efficacy of AG-1031 in the treatment of NSCLC in animal models and it remains of interest to further explore if we can offer a combinational therapy with above targeted drugs, including tyrosine inhibitors and monoclonal antibodies, to maximize the efficacy for NSCLC treatment.…”

“…Most recently, two monoclonal antibody-based drugs (nivolumab and pembrolizumab) that specifically target programmed cell death 1 (PD-1) were approved by the Food and Drug Adminstration for the treatment of advanced NSCLC following the first line therapy. Nevertheless, overall response rates to both agents were low [2], indicating that PD1-positive patients belong to a small group within the NSCLC population. The absence of targetable mutations in approximately 50% of NSCLC cases underscores the importance for developing alternative therapeutics for NSCLC treatment.…”

“…Several targeted agents have been explored recently, including the antagonists of epidermal growth factor receptor 6 (EGFR6) and vascular endothelial growth factor receptor (VEGFR), and inhibitors of anaplastic lymphoma kinase (ALK). However, despite their initial promise in cancer chemotherapy, the use of current anti-angiogenic drugs, including bevacizumab (anti-VEGF-A), endostatin (bFGF inhibitor) and crizotinib (ALK and ROS1 inhibitor), had very little impact on the treatment of NSCLC [2][3][4]. Most recently, two monoclonal antibody-based drugs (nivolumab and pembrolizumab) that specifically target programmed cell death 1 (PD-1) were approved by the Food and Drug Adminstration for the treatment of advanced NSCLC following the first line therapy.…”

Development of Antibody–Drug Conjugates Using DDS and Molecular Imaging

“…The antibody was labeled with a positron-emitting radionuclide as a tracer. The PET system can enable visualization of the antibody delivery from pairs of gamma rays emitted indirectly by the labeled tracer [ 33 ]. This immuno-PET is better than fluorescent imaging for deep tissue imaging because of its high sensitivity and accurate quantification.…”

The Analysis of Anticancer Drug Sensitivity of Lung Cancer Cell Lines by using Machine Learning Clustering Techniques

“…Most lung cancers originate in the lung carcinomas (epithelial tissue of the internal organs) and divide into nonsmall-cell lung cancer (NSCLC) [7], [8] and small-cell lung cancer (SCLC) [9]. SCLC is a critical type of lung cancer, caused by smoking and also responsible for diagnosing cases [10].…”