Emerging Molecular Dependencies of Mutant EGFR-Driven Non-Small Cell Lung Cancer

Farnsworth, Dylan; Chen, Yankuan T.; Yuswack, Georgia de Rappard; Lockwood, William W.

doi:10.3390/cells10123553

Cited by 11 publications

(3 citation statements)

References 135 publications

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“…6). Such expression pattern of ErbB-1 induces higher proliferative capacity, increased vessel density, cellular atypias, high mitotic activity, and distinctive infiltrative phenotype in both types of tissues, and these changes may bring forth their oncogenic potential [57,[60][61][62][63][64][65]. The observed cytoplasmic and nuclear distribution of ErbBs, especially for ErbB-1 and ErbB-3, besides their membranous localization in the eutopic endometrium during endometriosis may trigger pathogenic potential of eutopic endometrium [66][67][68][69][70].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ErbB-1 (EGFR) Protein in Eutopic Endome-Trium of Infertile Women with Severe Ovarian Endometriosis during the ‘Implantation Window’ of Menstrual Cycle

Poorasamy¹,

Garg²,

Bharti³

et al. 2022

Preprint

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Several lines of evidence indicate that high proliferative bias in eutopic endometrium during secretory phase is a hallmark of endometriosis and that high occurrence of implantation failure in patients resulting in infertility is often associated with endometriosis. ErbB family of proteins, which regulate the proliferation capacity in mammalian cells, appear as potential group of proteins to cause higher proliferation and endometrial hostility to implantation process in endometriosis. However, we have no concrete knowledge regarding the involvement of ErbB family in human endometrium during the ‘implantation window’, i.e., days 20-24 of a typical ovulatory cycle in endometriosis associated infertility. In the present study, the cellular profiles of immunopositive ErbBs-1 to -4 in endometrium of endometriosis-free, infertile women (Group 1; n=11), and in eutopic endometrium of infertile women diagnosed with stage IV ovarian endometriosis (Group 2; n=13) during mid-secretory phase were examined and compared using standardized WERF EPHect guidelines. Computer-aided standardized combinative analysis of immunoprecipitation in different compartments revealed an overexpression of ErbB-1 in the epithelial, stromal and vascular compartments along with marginally higher ErbB-3 expressions (P< 0.06) in the vascular compartment and ErbB-4 expression (P< 0.05) in the glandular epithelium and stroma in endometrium during the window of implantation of women with primary infertility associated with stage IV ovarian endometriosis compared with disease-free endometrium from women. A global overexpression of ErbB-1 in the endometrium during implantation window may induce anomalous proliferative, inflammatory and angiogenic activities in it, which antagonizes endometrial preparation for embryo implantation.

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Section: Discussionmentioning

confidence: 99%

Overexpression of ErbB-1 (EGFR) Protein in Eutopic Endome-Trium of Infertile Women with Severe Ovarian Endometriosis during the ‘Implantation Window’ of Menstrual Cycle

Poorasamy¹,

Garg²,

Bharti³

et al. 2022

Preprint

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“…Studies have shown that autophagy allows cancer cells to improve their survival at advanced stages or under therapeutic stress [181][182][183], which ultimately results in small-molecule targeted anticancer drug resistance. On the other hand, fibroblast growth factor receptor 1 (FGFR1) is commonly expressed in all types of cancer and is involved in tumor progression and epithelial-to-mesenchymal transition-related drug resistance to EGFR-TKIs [184][185][186][187]. Thinking together, inhibition of both FGFR1 and autophagy might be an effective method to surmount AZD9291 resistance.…”

Section: Nanomedicines To Overcome Targeted Therapy Resistancementioning

confidence: 99%

Nanomedicines for Overcoming Cancer Drug Resistance

Gong

et al. 2022

Pharmaceutics

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Clinically, cancer drug resistance to chemotherapy, targeted therapy or immunotherapy remains the main impediment towards curative cancer therapy, which leads directly to treatment failure along with extended hospital stays, increased medical costs and high mortality. Therefore, increasing attention has been paid to nanotechnology-based delivery systems for overcoming drug resistance in cancer. In this respect, novel tumor-targeting nanomedicines offer fairly effective therapeutic strategies for surmounting the various limitations of chemotherapy, targeted therapy and immunotherapy, enabling more precise cancer treatment, more convenient monitoring of treatment agents, as well as surmounting cancer drug resistance, including multidrug resistance (MDR). Nanotechnology-based delivery systems, including liposomes, polymer micelles, nanoparticles (NPs), and DNA nanostructures, enable a large number of properly designed therapeutic nanomedicines. In this paper, we review the different mechanisms of cancer drug resistance to chemotherapy, targeted therapy and immunotherapy, and discuss the latest developments in nanomedicines for overcoming cancer drug resistance.

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“…Interestingly. prolonged activation of EGFR enhances the dependence of lung tumor cells on EGFR signaling [ 6 ]. Additionally, several members of the EGFR family are often co-expressed with the RTK c-Met in various human cancers, and c-Met supports the proliferation and survival of non-small cell lung cancer (NSCLC) cells [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling

Lin,

Chang,

Liao

et al. 2024

Cell Death Discov.

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DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation. Knockdown of DUSP22 using shRNA enhances EGFR dependency in HCC827 lung cancer cells and increases sensitivity to gefitinib, an EGFR inhibitor. Consistently, genetic deletion of DUSP22 enhances EGFRdel (exon 19 deletion)-driven lung tumorigenesis and elevates EGFR activity. Pharmacological inhibition of DUSP22 activates EGFR, ERK1/2, and upregulates downstream PD-L1 expression. Additionally, lentiviral deletion of DUSP22 by shRNA enhances lung cancer cell migration through EGFR/c-Met and PD-L1-dependent pathways. Gefitinib, an EGFR inhibitor, mechanistically suppresses migration induced by DUSP22 deletion and inhibits c-Met activity. Furthermore, cabozantinib, a c-Met inhibitor, reduces migration and attenuates EGFR activation caused by DUSP22 deletion. Collectively, our findings support the hypothesis that loss of DUSP22 function in lung cancer cells confers a survival advantage by augmenting EGFR signaling, leading to increased activation of downstream c-Met, ERK1/2, and PD-L1 axis, ultimately contributing to the progression of advanced lung cancer.

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Emerging Molecular Dependencies of Mutant EGFR-Driven Non-Small Cell Lung Cancer

Cited by 11 publications

References 135 publications

Overexpression of ErbB-1 (EGFR) Protein in Eutopic Endome-Trium of Infertile Women with Severe Ovarian Endometriosis during the ‘Implantation Window’ of Menstrual Cycle

Overexpression of ErbB-1 (EGFR) Protein in Eutopic Endome-Trium of Infertile Women with Severe Ovarian Endometriosis during the ‘Implantation Window’ of Menstrual Cycle

Nanomedicines for Overcoming Cancer Drug Resistance

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling

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