Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer

Ruíz-Cordero, Roberto; Devine, W. Patrick

doi:10.1016/j.path.2019.11.002

Cited by 312 publications

(235 citation statements)

References 93 publications

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“…Advancements in screening technologies along with prophylactic screens of high-risk populations have significantly improved outcomes through identification of pre-invasive tumors ( Barletta et al, 2017 ). In addition, the development of precision therapies and immunotherapies for lung adenocarcinomas have improved 5-year survival rates by targeting the root causes of the disease ( Ruiz-Cordero & Devine, 2020 ). Despite these advances, only 25% of LSCC diagnoses are at an early-stage when the disease is localized ( Blandin Knight et al, 2017 ), and treatments lag far behind lung adenocarcinomas ( Leukam & Villaflor, 2015 ) demonstrating a collective lack of knowledge surrounding the disease.…”

Section: Discussionmentioning

confidence: 99%

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

Dong

Zhu

Zhang

2020

PeerJ

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Background Squamous cell carcinomas of the lung are an extremely common and deadly form of non-small cell lung cancers. Clinical management of the disease is dependent on staging and metastatic status. Metastasis to the lymph node is especially crucial to diagnose as it occurs at an earlier stage. However, lymphadenectomies are invasive and tumor cells may be overlooked during evaluation.There are limited approved biomarkers for predicting lymph node metastasis with squamous cell carcinomas of the lung (LSCC). Methods Genome data of 60 tumor-adjacent samples were downloaded from Genome Expression Omnibus. We identified over-expressed HUB genes using Cytoscape as key prognostic markers. The selected markers were further evaluated based on gene ontology and overall expression levels compared to normal tissue using The Cancer Genome Atlas. We further validated these results using clinical biopsy tissue taken from squamous cell carcinoma patients. Results Analysis of the genome expression data resulted in 13 relevant hub genes that were differentially expressed in cancerous samples. All of these genes are associated with collagen biosynthesis within the tumor microenvironment. We chose Collagen Type 1 Alpha 1 (COL1A1) as the most relevant prognostic marker due to its high number of pathway connections and over expression in the tumor microenvironment compared to the other 12 genes. Additionally, based on analysis of The Cancer Genome Atlas, tumors with higher levels of COL1A1 expression are associated with poorer overall survival. Finally, evaluation of clinical biopsy samples suggests that overexpression of COL1A1 in the LSCC microenvironment highly correlates with lymph node metastasis. These results suggest COL1A1 is a clinically relevant marker that should be used to justify lymphadenectomies.

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Section: Discussionmentioning

confidence: 99%

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

Dong

Zhu

Zhang

2020

PeerJ

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“…3 Recent years have witnessed great progress in the treatment of NSCLC with molecular and targeted drugs, rendering advanced NSCLC the most successfully treated type of cancer in precision medicine. 4 Drugs targeting EGFR, ALK, ROS1, and BRAF and other positive driver genes have provided significant survival benefits for the patients. 5 Studies have suggested that approximately 80% of patients with NSCLC were diagnosed with advanced or metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

<p>Influence of Programmed Death Ligand-1-Gene Polymorphism rs822336 on the Prognosis and Safety of Postoperative Patients with NSCLC Who Received Platinum-Based Adjuvant Chemotherapy</p>

Zhao¹,

Zhang²,

Chen

et al. 2020

CMAR

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This study was done to investigate the influence of PDL1-gene polymorphism on the prognosis and safety of postoperative patients with non-small cell lung cancer (NSCLC) who had received platinum-based adjuvant chemotherapy. Methods: A total of 289 postoperative patients with NSCLC who had received platinumbased adjuvant chemotherapy from January 2012 to June 2019 participated in this study. Recurrence status and adverse reactions were documented during adjuvant chemotherapy. Overall survival (OS) data were obtained through telephone follow-up. DNA extracted from hematologic specimens was genotyped for PDL1-gene polymorphism. Associations between genotype status and prognosis were assessed using Kaplan-Meier survival analysis, and multivariate adjustment was performed using Cox regression analysis. Results: Median disease-free survival of the 289 patients with NSCLC was 3.3 years and median OS 4.9 years. With regard to the PDL1 gene polymorphism, only rs822336 was of clinical significance in the subsequent analysis. The minor-allele frequency of rs822336 was 0.21, and distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (P=0.807). Survival analysis according to genotype status suggested that median disease-free survival of patients with GG and GC/CC genotypes was 2.8 and 4.1 years, respectively (P=0.01). Median OS of patients with GG and GC/CC genotypes was 4.1 and 5.4 years, respectively (P=0.008). However, the safety analysis failed to find a significant association between the polymorphism and adverse reactions. Interestingly, expression analysis of RNA extracted from peripheral blood mononuclear cells indicated that PDL1-mRNA expression of patients with the GG genotype was significantly higher than for the GC/CC genotype (P<0.001). Conclusion: The prognosis of postoperative patients with NSCLC who have received platinum-based adjuvant chemotherapy may be influenced by the rs822336 polymorphism through mediation of the mRNA expression of PDL1.

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“…Most NSCLC drug therapies target tyrosine kinases in several signal transduction pathways [26][27][28]. Several drugs have been approved for treatment of NSCLC [29,30].…”

Section: Epidermal Growth Factor Receptor (Egfr)mentioning

confidence: 99%

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

Hamid

Petreaca

2020

Cancers

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Secondary resistant mutations in cancer cells arise in response to certain small molecule inhibitors. These mutations inevitably cause recurrence and often progression to a more aggressive form. Resistant mutations may manifest in various forms. For example, some mutations decrease or abrogate the affinity of the drug for the protein. Others restore the function of the enzyme even in the presence of the inhibitor. In some cases, resistance is acquired through activation of a parallel pathway which bypasses the function of the drug targeted pathway. The Catalogue of Somatic Mutations in Cancer (COSMIC) produced a compendium of resistant mutations to small molecule inhibitors reported in the literature. Here, we build on these data and provide a comprehensive review of resistant mutations in cancers. We also discuss mechanistic parallels of resistance.

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Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer

Cited by 312 publications

References 93 publications

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

<p>Influence of Programmed Death Ligand-1-Gene Polymorphism rs822336 on the Prognosis and Safety of Postoperative Patients with NSCLC Who Received Platinum-Based Adjuvant Chemotherapy</p>

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

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