Oncogenic driver mutations in non-small cell lung cancer: Past, present and future

Chevallier, Mathieu; Borgeaud, Maxime; Addeo, Alfredo; Friedlaender, Alex

doi:10.5306/wjco.v12.i4.217

Cited by 157 publications

(101 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The findings of whole-exome sequencing analysis also indicated that EREG expression is induced in oncogenic KRAS-driven PDAs [ 94 ]. Notably, the oncogenic driver mutations, such as EGFR and KRAS, are commonly observed in lung adenocarcinoma [ 95 ]. Moreover, tumor-promoting functions were blocked by anti-EREG antibodies or an EGFR-tyrosine kinase inhibitor (EGFR-TKI, gefitinib or erlotinib) in NSCLC [ 80 ].…”

Section: The Expression Levels Of Ereg During Cancer Progressionmentioning

confidence: 99%

The Role of EREG/EGFR Pathway in Tumor Progression

Cheng

Feng

Lee

et al. 2021

IJMS

109

View full text Add to dashboard Cite

Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung cancer and colorectal cancer (CRC). Epiregulin (EREG) is one of the EGFR ligands and is low expressed in most normal tissues. Elevated EREG in various cancers mainly activates EGFR signaling pathways and promotes cancer progression. Notably, a higher EREG expression level in CRC with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) is related to better efficacy of therapeutic treatment. By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations. Additionally, EREG overexpression in non-small cell lung cancer (NSCLC) is anticipated to be a therapeutic target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that EREG derived from macrophages promotes NSCLC cell resistance to EGFR-TKI treatment. The emerging events of EREG-mediated tumor promotion signals are generated by autocrine and paracrine loops that arise from tumor epithelial cells, fibroblasts, and macrophages in the tumor microenvironment (TME). The TME is a crucial element for the development of various cancer types and drug resistance. The regulation of EREG/EGFR pathways depends on distinct oncogenic driver mutations and cell contexts that allows specific pharmacological targeting alone or combinational treatment for tailored therapy. Novel strategies targeting EREG/EGFR, tumor-associated macrophages, and alternative activation oncoproteins are under development or undergoing clinical trials. In this review, we summarize the clinical outcomes of EREG expression and the interaction of this ligand in the TME. The EREG/EGFR pathway may be a potential target and may be combined with other driver mutation targets to combat specific cancers.

show abstract

Section: The Expression Levels Of Ereg During Cancer Progressionmentioning

confidence: 99%

The Role of EREG/EGFR Pathway in Tumor Progression

Cheng

Feng

Lee

et al. 2021

IJMS

109

View full text Add to dashboard Cite

show abstract

“…In the last two decades, targetable gene alterations have been identified in about 45% of patients with non-small-cell lung cancers (NSCLC) [ 49 ]. In particular, EGFR mutations or ALK-EML4 translocations are identified in up to 50% of non-smokers or Asian patients with NSCLC of the adenocarcinoma histological sub-type [ 50 ].…”

Section: Tyrosine Kinase Inhibitors For the Treatment Of Lung Cancer Brain Metastasesmentioning

confidence: 99%

Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier

Angeli

Bousquet

2021

Pharmaceutics

View full text Add to dashboard Cite

The incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood–brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of cancer have led to the identification of numerous molecular alterations, some of them targetable with the development of specific targeted therapies, including tyrosine kinase inhibitors. In this narrative review, we set out to describe the state-of-the-art in the use of tyrosine kinase inhibitors for the treatment of melanoma, lung cancer, and breast cancer brain metastases. We also report preclinical and clinical pharmacological data on brain exposure to tyrosine kinase inhibitors after oral administration and describe the most recent advances liable to facilitate their penetration of the blood–brain barrier at relevant concentrations and limit their physiological efflux.

show abstract

“…It is well established that certain mutations in critical genes initiate tumorigenesis and confer an invasive phenotype to lung cancer cells. Although a significant portion (~50%) of NSCLCs are linked to mutations in KRAS and EGFR, other implicated genes include BRAF (5%), ALK (3%), MET (3%), and HER2 (3%) [ 7 ]. STK11/LKB1 was first discovered and recognized as an important tumor suppressor gene in the 1990s after analyzing the genomic sequence of patients with Peutz-Jeghers syndrome [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Role of STK11/LKB1 in Non-small Cell Lung Cancer

Sumbly¹,

Landry²

2022

Cureus

View full text Add to dashboard Cite

There are two major groups of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLCs can be further separated into three different categories: lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Pulmonary adenocarcinomas represent nearly half of all lung cancer cases and are known to be caused by smoking, certain occupational exposures, and specific genetic mutations. Scientists have noticed that most NSCLCs are driven by defects in the following genes: EGFR, BRAF, ALK, MET, and HER. Abnormalities in the STK11/LKB1 gene have also been shown to induce lung adenocarcinoma. LKB1-deficient cancer cells contain an overactive AMPK "energy sensor," which inhibits cellular death and promotes glucose, lipid, and protein synthesis via the mTOR protein complex. Studies have also discovered that the loss of STK11/LKB1 favors oncogenesis by creating an immunosuppressive environment for tumors to grow and accelerate events such as angiogenesis, epithelial-mesenchymal transition (EMT), and cell polarity destabilization. STK11/LKB1-mutant lung cancers are currently treated with radiotherapy with or without chemotherapy. Recent clinical trials studying the effects of glutaminase inhibitors, mTOR inhibitors, and anti-PD-L1 therapy in lung cancer patients have yielded promising results. This narrative review provides an overview of the STK11/LKB1 gene and its role in cancer development. Additionally, a summary of the LKB1/APMK/mTOR is provided.

show abstract

Oncogenic driver mutations in non-small cell lung cancer: Past, present and future

Cited by 157 publications

References 126 publications

The Role of EREG/EGFR Pathway in Tumor Progression

The Role of EREG/EGFR Pathway in Tumor Progression

Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier

Unraveling the Role of STK11/LKB1 in Non-small Cell Lung Cancer

Contact Info

Product

Resources

About