scholarly journals Liquid Biopsy Biomarkers for Immunotherapy in Non-Small Cell Lung Carcinoma: Lessons Learned and the Road Ahead

2021 ◽  
Vol 11 (10) ◽  
pp. 971
Author(s):  
Jesus Hita-Millan ◽  
Angel Carracedo ◽  
Ceres Fernandez-Rozadilla
Keyword(s):  
Liquid Biopsy ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Significant Proportion ◽  
Small Cell ◽  
Lessons Learned ◽  
Small Cell Lung ◽  
Secondary Resistance ◽  
Cell Lung Carcinoma ◽  
The Road

Over the recent years, advances in the development of anti-cancer treatments, particularly the implementation of ICIs (immune checkpoint inhibitors), have resulted in increased survival rates in NSCLC (non-small cell lung cancer) patients. However, a significant proportion of patients does not seem respond to immunotherapy, and some individuals even develop secondary resistance to treatment. Therefore, it is imperative to correctly identify the patients that will benefit from ICI therapy in order to tailor therapeutic options in an individualised setting, ultimately benefitting both the patient and the health system. Many different biomarkers have been explored to correctly stratify patients and predict response to immunotherapy, but liquid biopsy approaches have recently arisen as an interesting opportunity to predict and monitor treatment response due to their logistic accessibility. This review summarises the current data and efforts in the field of ICI response biomarkers in NSCLC patients and highlights advantages and limitations as we discuss the road to clinical implementation.

scholarly journals Immunocheckpoint Inhibitor- (Nivolumab-) Associated Hypereosinophilia in Non-Small-Cell Lung Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Navdeep Singh ◽  
Sandeep Singh Lubana ◽  
George Constantinou ◽  
Andrea N. Leaf
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Lung Carcinoma ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Eosinophil Counts

Immunocheckpoint inhibitor (ICI) therapy has provided significant clinical improvements in the treatment of several malignancies. The purpose of this report is to increase awareness of hypereosinophilia associated with checkpoint inhibitors, a topic that has been rarely reported. Hypereosinophilia may need to be addressed especially if eosinophil counts increase to levels where hypereosinophilic visceral complications can occur. We are presenting a case of a 57-year-old male with hypereosinophilia that was seen in the setting of progression of metastatic non-small-cell lung cancer during and after nivolumab treatment.

scholarly journals Deep and Prolonged Response to Aurora A Kinase Inhibitor and Subsequently to Nivolumab in MYCL1-Driven Small-Cell Lung Cancer: Case Report and Literature Review

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Bhaskar C. Kolla ◽  
Emilian Racila ◽  
Manish R. Patel
Keyword(s):  
Kinase Inhibitor ◽  
Small Cell Lung Carcinoma ◽  
Significant Proportion ◽  
Small Cell ◽  
Cancer Case ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Tumor Immune Evasion

Small-cell lung carcinoma (SCLC) is one of the most aggressive solid tumors, and the prognosis has not improved significantly in 25 years. Despite a recent understanding of the genomic aberrations seen in SCLC, these insights have not led to any breakthroughs in treatment. We present a patient with SCLC harboring a novel MYCL1 fusion protein who experienced a prolonged disease course due to the use of Aurora A kinase inhibitor and subsequently nivolumab. MYC family genes are master regulators of several cellular pathways including proliferation, differentiation, and apoptosis and recently have been shown to be involved in tumor immune evasion. Large studies have shown that a significant proportion of patients with SCLC have amplification or overexpression of MYC family genes. Preclinical data have exposed vulnerability of MYC-driven tumors to Aurora kinase inhibitors, bromodomain and extraterminal domain inhibitors, and recently to immune checkpoint blockers. Further studies using these agents with selective enrolling of patients with MYC-altered tumors are warranted to exploit these vulnerabilities.

scholarly journals Challenges of Immunotherapy in Stage IV Non–Small-Cell Lung Cancer

2021 ◽  
pp. OP.20.00949
Author(s):  
Sophie Stock-Martineau ◽  
Kate Magner ◽  
Kevin Jao ◽  
Paul Wheatley-Price
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Programmed Death

Treatment for metastatic non–small-cell lung carcinoma has seen important advances in recent years with the introduction of targeted therapies and immunotherapy. Immune checkpoint inhibitors, which target the programmed death 1 receptor and programmed death ligand-1, alone or in combination with platinum-based chemotherapy, have become standard of care in the first-line setting for patients with advanced non–small-cell lung carcinoma without targetable driver mutations. However, several clinical questions have now since emerged. Physicians treating lung cancer lack guidance when treating patients who have a poor performance status, patients who are receiving corticosteroids, and those known for pre-existing autoimmune disorders. Furthermore, data are scarce on rechallenging a patient with immune checkpoint inhibitors after the occurrence of a significant immune-related adverse event. In this review, we aim to shed light on these topics.

scholarly journals Final amendment: A plausible explanation for in silico reporting of erroneous MET gene expression in tumor-educated platelets (TEP) intended for "liquid biopsy" of non-small cell lung carcinoma still refutes the TEP-study

2017 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Gene Expression ◽  
Lung Carcinoma ◽  
Liquid Biopsy ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Rna Seq ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Over Expression ◽  
Link Type

AbstractFinal amendment noteThis paper had proposed a plausible way for detecting large quantities of MET, which the authors have clarified was not done :the possible explanation proposed for this erroneous MET gene expression does bypass the filtering step we perform in the data processing pipeline, i.e. selection of intron-spanning reads, as can be read in the main text” comments in http://www.biorxiv.org/content/early/2017/07/02/146134, where a continuing critique of the TEP study continues. Please consider this pre-print closed.Original abstractThe reported over-expression of MET genes in non-small cell lung carcinoma (NSCLC) from an analysis of the RNA-seq data from tumor-educated platelets (TEP), intended to supplement existing ‘liquid biopsy’ techniques [1], has been refuted recently (http://biorxiv.org/content/early/2017/06/05/146134, not peer-reviewed). The MET proto-oncogene (Accid:NG 008996.1, RefSeqGene LRG 662 on chromosome 7, METwithintrons) encodes 21 exons resulting in a 6710 bps MET gene (Accid: NM 001127500.2, METonlyexons). METwithintrons has multiple matches in the RNA-seq derived reads of lung cancer samples (for example: SRR1982756.11853382). Unfortunately, these are non-specific sequences in the intronic regions, matching to multiple genes on different chromosomes with 100% identity (KIF6 on chr6, COL6A6 on chr3, MYO16 on chr13, etc. for SRR1982756.11853382). In contrast, METonlyexons has few matches in the reads, if at all [2]. However, even RNA-seq from healthy donors have similar matches for METwithintrons so the computation behind the over-expression statistic remains obscure, even if METwithintrons was used as the search gene. In summary, this work re-iterates the lack of reproducibility in the bioinformatic analysis that establishes TEP as a possible source for “liquid biopsy”.

scholarly journals Immune checkpoint inhibitors for the management of advanced non–small-cell lung carcinoma

2020 ◽  
Vol 31 (6) ◽  
pp. 637-645 ◽  
Author(s):  
Li-ting Lai ◽  
Zheng-yu Zhan ◽  
Miao Feng ◽  
Fan Li ◽  
Lin-feng Lai ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma
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