Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer

Coleman, Niamh; Hong, Lingzhi; Zhang, J.; Heymach, John V.; Hong, David S.; Le, Xiuning

doi:10.1016/j.esmoop.2021.100319

Cited by 66 publications

(49 citation statements)

References 96 publications

(147 reference statements)

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“…P-gp, a well-known multidrug resistance protein, encoded by MDR1, it serve as medicine pump by reverse the concentration of lipophilic drugs with positive charge inside the cell to the outside of the cell, so that the intracellular chemotherapy drugs can not reach the effective concentration and develop drug resistance ( Robey et al, 2018 ). In non-small-cell-lung cancer, MET amplification is thought to be responsible for resistance to targeted drugs in EGFR-mutation-positive patients, which results in malignant biological behavior of tumors, such as invasion, metastasis, escape from apoptosis ( Coleman et al, 2021 ). Combining with the C1QTNF6 expression and its drug sensitivity analysis (positively correlated and negatively correlated), we may establish risk stratification for cancer patients, which optimize the development and application of anti-cancer drugs.…”

Section: Discussionmentioning

confidence: 99%

C1QTNF6 is a Prognostic Biomarker and Related to Immune Infiltration and Drug Sensitivity: A Pan-Cancer Analysis

et al. 2022

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Background: The discovery of reliable cancer biomarkers could tune a diagnosis and improve the way patients are treated. However, many cancers lack robust biomarkers. C1QTNF6 has been preliminarily elucidated for its role in some tumors. However, no pan-cancer analysis has been performed to comprehensively explore the value of C1QTNF6.Methods: Data from the TCGA database, GTEx database stored in the USUC Xena were used for analyzing the profiles of C1QTNF6 expression in normal and tumor tissues in pan-cancer. Subsequently, the gene alteration rates of C1QTNF6 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between C1QTNF6 mRNA expression and copy number alterations (CNA) and methylation was determined. Survival analyses of C1QTNF6 were carried out. Moreover, the tumor biological and immunological characteristics of C1QTNF6 were clarified in the forms of the correlation between C1QTNF6 expression and hallmark Pathway scores in MsigDB database, immune cell infiltration, immune-related genes. We conducted a GSEA of C1QTNF6 to illustrate its potential biological functions. In addition, GDSC2 data with 198 drugs were adopted to explore drug sensitivity with the change of C1QTNF6 expression.Result:C1QTNF6 was overexpressed in many types of cancer, Survival analysis showed that C1QTNF6 independently served as a prognostic indicator for poor survival in many tumors. Besides, we also identified a positive correlation between C1QTNF6 and cancer hallmark pathway score, tumor microenvironment related pathways score (TMEp score), and immune characteristic. In terms of drug sensitivity analysis, we found higher expression level of C1QTNF6 predicts a high IC50 value for most of 198 drugs which predicts drug resistance.Conclusions: Our study provides a new biological marker for pan-cancer, which is beneficial to the diagnosis and treatment of cancer, which bring a new therapeutic target for tumors.

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Section: Discussionmentioning

confidence: 99%

C1QTNF6 is a Prognostic Biomarker and Related to Immune Infiltration and Drug Sensitivity: A Pan-Cancer Analysis

et al. 2022

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“…However, not all NGS-based assays control for CEP7; consequently, a detected increase in copy number may actually be a polysomy instead of a proper MET amplification. [41]. Therefore, FISH is advised if NGS does not expressly assess for gene copy number gain [42].…”

Section: Egfr Off-target Alteration 221 Met Amplificationmentioning

confidence: 99%

Acquired Resistance to Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer: How Do We Overcome It?

Bertoli

Carlo

Conte

et al. 2022

IJMS

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Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutation and the standard second-line therapy in T790M-positive patients in progression to previous EGFR tyrosine kinase inhibitor. Osimertinib is a highly effective treatment that shows a high response rate and long-lasting disease control. However, a resistance to the treatment inevitably develops among patients. Understanding the secondary mechanisms of resistance and the possible therapeutic options available is crucial to define the best management of patients in progression to osimertinib. We provide a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre-treated with osimertinib and its future treatment applications.

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“…85 The most common off-target mechanism of resistance bypassing the EGFR inhibition pathway is represented by MET amplification (10-15%), 86 leading to the activation of the downstream AKT pathway, which is the key signalling pathway for cell proliferation and antiapoptosis. 87 The amplification of the ErbB2 gene has been found in 12% of cases of resistance to first-generation and second-generation EGFR-TKIs and in about 2% of cases of resistance to osimertinib. Moreover, FGFR, BRAF, KRAS and PIK3CA mutations could lead to resistance to EGFR-TKIs from first, second and third generations, conferring survival advantages to cancer cells.…”

Section: Mechanisms Of Resistance To Egfr-tkismentioning

confidence: 99%

Non-small-cell lung cancer: how to manage EGFR-mutated disease

Pecci¹,

Cantini²,

Metro³

et al. 2022

DIC

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The treatment of non-small-cell lung cancer (NSCLC) harbouring EGFR mutations has witnessed some major breakthroughs in the last years. On the one hand, the recent advent of the third-generation tyrosine kinase inhibitor (TKI) osimertinib has reshaped the therapeutic algorithm both in the first-line and adjuvant settings for patients with common activating Ex19del and L858R EGFR mutations. On the other hand, the availability of new comprehensive next-generation sequencing panels, to be used on tumour tissue or on liquid biopsy, has revealed the existence of uncommon as well as compound mutations that partially explain the onset of resistance. Nevertheless, dissecting the biological mechanisms underlying primary and secondary resistance to EGFR-TKIs is crucial to developing alternative therapeutic strategies and further improving patient outcomes. Herein, we provide an updated and comprehensive summary of the latest advancements in the quest for compounds targeting EGFR -mutant advanced non-small-cell lung cancer, discussing the biological rationale underlying the development of a forefront combination of TKI and/or new antibody–drug conjugates. We also suggest a treatment algorithm that could be followed considering the latest published data.

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Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer

Cited by 66 publications

References 96 publications

C1QTNF6 is a Prognostic Biomarker and Related to Immune Infiltration and Drug Sensitivity: A Pan-Cancer Analysis

C1QTNF6 is a Prognostic Biomarker and Related to Immune Infiltration and Drug Sensitivity: A Pan-Cancer Analysis

Acquired Resistance to Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer: How Do We Overcome It?

Non-small-cell lung cancer: how to manage EGFR-mutated disease

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