Molecular Drivers in Lung Adenocarcinoma: Therapeutic Implications

2020 ◽  
pp. 185-206
Author(s):  
Imayavaramban Lakshmanan ◽  
Apar Kishor Ganti
Keyword(s):  
Lung Adenocarcinoma ◽  
Therapeutic Implications

scholarly journals PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma

2020 ◽  
Vol 12 (527) ◽  
pp. eaax3772 ◽  
Author(s):  
Xiaochao Tan ◽  
Priyam Banerjee ◽  
Edward A. Pham ◽  
Florentine U. N. Rutaganira ◽  
Kaustabh Basu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Survival ◽  
Cancer Cell ◽  
Secretory Vesicle ◽  
Effector Proteins ◽  
Therapeutic Implications ◽  
Chromosome 1Q ◽  
Biological Studies ◽  
Cancer Cell Survival ◽  
Vesicle Biogenesis

Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)–dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

Prognostic value and therapeutic implications of expanded molecular testing for resected early stage lung adenocarcinoma

Lung Cancer ◽  
2020 ◽  
Vol 143 ◽  
pp. 60-66 ◽  
Author(s):  
Peter J. Kneuertz ◽  
David P. Carbone ◽  
Desmond M. D’Souza ◽  
Konstantin Shilo ◽  
Mahmoud Abdel-Rasoul ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Early Stage ◽  
Molecular Testing ◽  
Therapeutic Implications

scholarly journals Integrative omics analysis identifies subtypes with therapeutic implications in lung adenocarcinoma harboring KEAP1/NFE2L2

2021 ◽  
Author(s):  
Xiaodong Yang ◽  
Ming Li ◽  
Zhencong Chen ◽  
Liang Guo ◽  
Bo Jin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Mutant Cell ◽  
The Cancer Genome Atlas ◽  
Immune Microenvironment ◽  
Bioinformatics Analyses ◽  
Therapeutic Implications ◽  
Genomic Aberrations ◽  
Public Datasets

Abstract Backgrounds: Lung adenocarcinoma is one of the most common malignant tumors, in which KEAP1-NFE2L2 pathway is altered frequently. The biological features and intrinsic heterogeneities of KEAP1/NFE2L2-mutant lung adenocarcinoma remain unclear. Methods: Multiplatform data from The Cancer Genome Atlas (TCGA) were adopted to identify two subtypes of lung adenocarcinoma harboring KEAP1/NFE2L2 mutations. Bioinformatics analyses, regarding immune microenvironment, methylation level and mutational signature, were performed to characterize intrinsic heterogeneities. Meanwhile, initial results were also validated by using common lung adenocarcinoma cell lines, which revealed consistent features of KEAP1/NFE2L2-mutant subtypes. Furthermore, cell line samples were adopted for drug sensitivity screening based on public datasets. Results: Two mutant subtypes (P1 and P2) of patients were identified in TCGA. P2 patients had significantly heavier smoking levels and worse survival compared with P1 patients. The P2 subset was characterized by active immune microenvironment and more smoking-induced genomic alterations, including methylation and somatic mutations. Validations of the corresponding features in mutant cell lines were achieved to some degrees. Several compounds which were sensitive to mutant subtype of lung adenocarcinoma were identified, such as inhibitors of PI3K/Akt and IGF1R signaling pathways. Conclusions: KEAP1/NFE2L2 mutant lung adenocarcinoma showed potential heterogeneities. The intrinsic heterogeneities of KEAP1/NFE2L2 were associated with immune microenvironment and smoking-related genomic aberrations.

Biomarkers in Lung Adenocarcinoma: A Decade of Progress

2014 ◽  
Vol 139 (4) ◽  
pp. 469-480 ◽  
Author(s):  
Lynette M. Sholl
Keyword(s):  
Lung Adenocarcinoma ◽  
Predictive Marker ◽  
Epidemiologic Studies ◽  
Molecular Biomarkers ◽  
Central Component ◽  
Tumor Type ◽  
Alk Rearrangement ◽  
Therapeutic Implications ◽  
Development Of Resistance ◽  
Targeted Inhibition

Context The analysis of molecular biomarkers in lung adenocarcinoma (ACA) is now a central component of pathologic diagnosis and oncologic care. The identification of an EGFR mutation or ALK rearrangement in advanced-stage lung ACA will dictate a change in first-line treatment from standard chemotherapy to targeted inhibition of these oncogenic alterations. Viable approaches to therapeutic targeting of KRAS-mutated ACA are now under investigation, raising the possibility that this too will become an important predictive marker in this tumor type. The recognized array of less common oncogenic alterations in lung ACA, including in the ROS1, RET, BRAF, and ERBB2 genes, is growing rapidly. The therapeutic implications of these findings are, in many cases, still under investigation. Objective To focus on the major molecular biomarkers in lung ACA, recommended testing strategies, the implications for targeted therapies, and the mechanisms that drive development of resistance. Data Sources Our current understanding of predictive and prognostic markers in lung ACA is derived from a decade of technical advances, clinical trials, and epidemiologic studies. Many of the newest discoveries have emerged from application of high-throughput next-generation sequencing and gene expression analyses in clinically and pathologically defined cohorts of human lung tumors. Conclusions Best practices require a solid understanding of relevant biomarkers for diagnosis and treatment of patients with lung ACA.

scholarly journals Integrative analysis reveals distinct subtypes with therapeutic implications in KRAS-mutant lung adenocarcinoma

EBioMedicine ◽  
2018 ◽  
Vol 36 ◽  
pp. 196-208 ◽  
Author(s):  
Ke Liu ◽  
Jintao Guo ◽  
Kuai Liu ◽  
Peiyang Fan ◽  
Yuanyuan Zeng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Integrative Analysis ◽  
Therapeutic Implications

scholarly journals Prognostic and Therapeutic Implications of EGFR and KRAS Mutations in Resected Lung Adenocarcinoma

2008 ◽  
Vol 3 (2) ◽  
pp. 111-116 ◽  
Author(s):  
Jenifer L. Marks ◽  
Stephen Broderick ◽  
Qin Zhou ◽  
Dhananjay Chitale ◽  
Allan R. Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kras Mutations ◽  
Therapeutic Implications

Abstract #619 Primary Lung Adenocarcinoma in a Sea of Metastatic Thyroid Cancer

2019 ◽  
Vol 25 ◽  
pp. 319-320
Author(s):  
Lourdes Rodriguez ◽  
Mary Baker ◽  
Daniel W Karakla ◽  
David Lieb
Keyword(s):  
Thyroid Cancer ◽  
Lung Adenocarcinoma ◽  
Primary Lung Adenocarcinoma ◽  
Metastatic Thyroid Cancer

WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis

2009 ◽  
Vol 138 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Don X. Nguyen ◽  
Anne C. Chiang ◽  
Xiang H.-F. Zhang ◽  
Juliet Y. Kim ◽  
Mark G. Kris ◽  
...  
Keyword(s):  
Lung Adenocarcinoma
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