Oncogene addiction and tumor mutational burden in non ‐small‐cell lung cancer: Clinical significance and limitations

AbstractLung cancer incidence has increased worldwide over the past decades, with non ‐small cell lung cancer (NSCLC) accounting for the vast majority (85%) of lung cancer specimens. It is estimated that lung cancer causes about 1.7 million global deaths per year worldwide. Multiple trials have been carried out, with the aim of finding new effective treatment options. Lately, speci al focus has been placed on immune checkpoint (PD1/PD‐L1) inhibitors which impact the tumor immune microenvironment. Tumor mutational burden (TMB) has been found to predict response to immune checkpoint inhibitors. Conversely, recent studies have weakened the significance of TMB as a predictor of response to therapy and survival. In this review article, we discuss the significance of TMB, as well as possible limitations. Furthermore, we give a concise overview of mutations frequently found in NSCLC, and discuss the significance of oncogene addiction in lung cancer as an essential driver of t umorigenesis and tumor progression.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: MINI REVIEW Source Type: research

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In the past decades, the panorama of molecular diagnostics and care of non-small cell lung cancer (NSCLC) has rapidly evolved. The discovery of novel drivers for oncogene addiction has led to the development of additional therapeutic options in first as well as in subsequent lines. This, in turn, has fostered the search for robust and reliable molecular screening methods to support clinicians in prompt decision-making [1,2].
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
We report the case of a 53-year-old woman affected by metastatic anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer who received ALK tyrosine kinase inhibitors, from January 2017. The patient had a complete response of choroidal metastasis after therapy with ALK tyrosine kinase inhibitors. She recovered a complete visus and actually she still continue therapy with alectinib. The patient had a complete recovery of visus in addiction to a long response on treatment.
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports Source Type: research
Purpose of review Recently, the combination of antiangiogenic agents, chemotherapy and immunotherapy has shown synergistic anticancer effects in non-small cell lung cancer (NSCLC). The future for this approach appears bright in lung cancer treatment; however, many challenges remain to be overcome regarding its true potential, optimal sequence and timing of therapy, and safety profile. In this review, we will discuss the current status and future direction of antiangiogenic therapy for the treatment of NSCLC, and highlight emerging strategies, such as tumor vessel normalization (TVN). Recent findings Bevacizumab was th...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research
AbstractBackgroundNon-small cell lung cancer (NSCLC) is one of the commonest disease worldwide and the leading cause of cancer-related death. Incidence increases with age and reaches a peak in senility, when patients ’ (pts) comorbidities may limit the efficacy of treatments. At this time, no homogeneous indications are available for elderly NSCLC pts and the optimization of treatment, with the lowest side effects, is still an unmet need, also after the introduction of innovative drugs. The ribonucleotide redu ctase catalytic subunit M1(RRM1), the DNA-excision repair protein ERCC1 and the thymidylate synthetase (TS) ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Roberto Bianco In the last few years, the treatment strategy in Non-Small Cell Lung Cancer (NSCLC) patients has been heavily modified by the introduction of the immune-checkpoint inhibitors. Anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy has improved both progression-free and the overall survival in almost all subgroups of patients, with or without PDL1 expression, with different degrees of responses. However, there are patients that are not benefitting from this treatment. A defined group of immune-checkpoint inhibitors non-responder tumours carry EGFR (epidermal growth factor recept...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Rossi A Abstract Introduction: Nonsquamous non-small-cell lung cancer (NSCLC) is divided in oncogene-addicted subgroups, highly expressed programmed death ligand-1 (PD-L1 ≥ 50%) subgroup, and "negative" subgroup. The latter represents the most common group comprising about 50% of all new diagnoses of nonsquamous NSCLC. For this group, chemotherapy was the standard approach with pemetrexed- and/or bevacizumab-based regimens reaching an overall survival of about 12-17 months. Areas covered: This review will focus on the new options for combination therapies, which have already recently arrived o...
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Tags: Expert Rev Respir Med Source Type: research
Brain is the most frequent site for distant metastases of non-small cell lung cancer (NSCLC). Brain metastasis (BM) is also the leading cause of disabilities and death in advanced NSCLC. In recent years, the application and effectiveness of small-molecule tyrosine kinase inhibitors has formed the basis for the treatment of NSCLC brain metastases with driver gene mutations. With the development of programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitors and relevant combination therapies, immunotherapy has become an important choice for non-classic oncogene addicted NSCLC BM patients....
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
Abstract Mutations in KEAP1 and NFE2L2 (encoding the protein Nrf2) are prevalent in both adenocarcinoma and squamous subtypes of non-small cell lung cancer. The consequence of these mutations is stabilized Nrf2 and chronic induction of several Nrf2 target genes. Here, downregulation of Nrf2 resulted in modest growth inhibition of cells growing in 2D; this was more pronounced in cell lines expressing mutant KEAP1. In contrast, downregulation of Nrf2 caused almost complete regression of established KEAP1-mutant tumors in mice, with little effect on wildtype (WT) KEAP1 tumors. The strong dependency on Nrf2 could be r...
Source: Genomics Proteomics ... - Category: Genetics & Stem Cells Authors: Tags: Cancer Res Source Type: research
Conclusion.NLR and PLR may predict the appearance of irAEs in non‐oncogene‐addicted aNSCLC, although this conclusion warrants prospective validation.Implications for Practice.This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune‐related adverse events (irAEs) in patients with advanced non‐small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Lung Cancer Source Type: research
Abstract ALK and ROS1 kinases have become promising therapeutic targets since Crizotinib was used to treat non-small-cell lung cancer clinically. Aiming to explore new potent inhibitors, a series of 2-amino-4-(1-piperidine) pyridine derivatives that stabilized a novel DFG-shifted conformation in the kinase domain of ALK were designed and synthesized on the base of lead compound A. Biological evaluation highlighted that most of these new compounds could also potently inhibit ROS1 kinase, leading to the promising inhibitors against both ROS1 and ALK. Among them, the representative compound 2e stood out potent anti-p...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
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