Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non-Small Cell Lung Cancer: A Review

Abstract

Advanced non‐small cell lung cancer (NSCLC) is a complex disease comprising molecularly distinct tumor types, each with a unique biology that is becoming increasingly better characterized. The aim of this review is to present an optimized treatment schema and the accompanying diagnostic testing approach for patients with advanced NSCLC. There are a number of therapies currently approved for patients with advanced NSCLC, including agents that target particular oncogenic drivers, as well as immune checkpoint blockers (ICBs) that elicit an antitumor response. Identification of genetic alterations (e.g., epidermal growth factor receptor, anaplastic lymphoma kinase, reactive oxygen species proto‐oncogene 1, B‐Raf proto‐oncogene) or programmed cell death ligand‐1 expression levels in NSCLC requires diligent molecular testing at initial diagnosis and, in some cases, at disease progression to ensure the most efficacious treatment is delivered. Accurate molecular diagnostic testing, along with the careful selection of currently approved targeted agents, ICBs, or systemic chemotherapy, provides therapy that is personalized according to patients’ needs to achieve the best possible outcome. Enrollment in clinical trials that further the development of tailored therapies is highly recommended at all stages of treatment. Implications for Practice Targeted therapies and immune checkpoint blockers provide effective and tailored options for patients with non‐small cell lung cancer. Careful molecular analysis of tumor samples is necessary to identify the genetic alterations that are present, to ensure that each patient receives the most efficacious treatment for their specific tumor type. Personalized therapy provides each patient with the best probability for prolonged survival. Enrolling patients in clinical trials should be the first consideration before making each treatment decision.

Extracellular Vesicles in Non-Small-Cell Lung Cancer: Functional Role and Involvement in Resistance to Targeted Treatment and Immunotherapy

“…Each single lung cancer is characterized by an average of 300 DNA mutations, while only a few genes are able to promote tumorigenesis [83]. The two main NSCLC drivers are EGFR and ALK, along with ROS1 and the met proto-oncogene (c-MET), and other genes that are less frequently altered [4,84]. EGFR tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, afatinib, and osimertinib, typically improve time to progression, response rates, and overall survival in EGFR-mutated patients, but acquired resistance to anti-EGFR TKIs is inevitable [85].…”

“…In the last ten years, treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of targeted and immunological therapies in clinical practice [1][2][3]. Currently, the use of tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK) are the first treatment of choice for patients carrying alterations in the EGFR and ALK genes, as well as for patients with alterations in the proto-oncogene tyrosine-protein kinase ROS-1 (ROS1) [4]. On the other side, immune-checkpoint inhibitors represent the first treatment of choice for patients with high expression of the programmed cell death ligand 1 (PD-L1), as monotherapy (pembrolizumab), or in combination with chemotherapy for those patients presenting with no targeted alterations (nivolumab or atezolizumab) [4].…”

“…Currently, the use of tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK) are the first treatment of choice for patients carrying alterations in the EGFR and ALK genes, as well as for patients with alterations in the proto-oncogene tyrosine-protein kinase ROS-1 (ROS1) [4]. On the other side, immune-checkpoint inhibitors represent the first treatment of choice for patients with high expression of the programmed cell death ligand 1 (PD-L1), as monotherapy (pembrolizumab), or in combination with chemotherapy for those patients presenting with no targeted alterations (nivolumab or atezolizumab) [4]. Although both types of treatment prolong progression free survival and improve patient prognosis, resistance mechanisms inevitably arise, leading to disease progression in almost all patients [5].…”

The construction of a lymphoma cell-based, DC-targeted vaccine, and its application in lymphoma prevention and cure

“…Following the development of oncology and immunology as sciences, the complexity of immune therapeutics in the immune system is exemplified by the myriad of ongoing investigations taking place in parallel [ 14 ]. Some immune therapeutics have been approved by the FDA and were successfully used in the clinic [ 15 , 16 ]. The representative immuno-therapeutic drug of NHL is rituximab, which targets the marker of CD20 of lymphoma cells.…”

“…The representative immuno-therapeutic drug of NHL is rituximab, which targets the marker of CD20 of lymphoma cells. The rituximab plus CHOP (a chemotherapy program) combination (R–CHOP) regimen indeed improved long-term outcomes of patients and has been used as the first-line treatment for many patients [ 16 ]. However, problems associated with chemotherapeutic drugs remain, namely the poor targeting capability and severe side effects, which result in a modest curative effect and harmful organism adaptation.…”