Inhibition of ACK1 delays and overcomes acquired resistance of EGFR mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib

Gu, Jian; Qian, Lu‐Xi; Zhang, Guojing; Mahajan, Nupam P.; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Sun, Shi Yong

doi:10.1016/j.lungcan.2020.09.023

Cited by 15 publications

(22 citation statements)

References 28 publications

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“…We classified the AR mechanisms into five categories: (a) aberration of EGFR itself, (b) activation of bypass signaling, (c) suppression of apoptosis, (d) EMT, and (e) other mechanisms. Mechanisms of acquired resistance to first-line osimertinib that were identified in cell line models [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]48,[50][51][52][53][54][55][56][57][58][59][60]. This graph is color-coded by cell line models and mechanisms of resistance to first-line osimertinib.…”

Section: Search Criteria For Published Studiesmentioning

confidence: 99%

“…Our search criteria included the following terms: “osimertinib,” “resistance,” “lung cancer,” and “cell line” or “cell lines.” We also manually scanned the reference lists of selected articles for additional eligible publications. We finally identified 29 relevant papers [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. We excluded 2 of these papers [ 47 , 49 ], as they used osimertinib-resistant cell lines that had been established in other studies included in our survey.…”

Section: Cell Line Models Used To Analyze Resistance Mechanisms Tomentioning

confidence: 99%

“…As AR mechanisms against first-line osimertinib, Src-mediated activation of AKT is reported as a mechanism of resistance in H1975 cells [ 35 ]. Another group reported that increased ACK1, which phosphorylates AKT and activates the AKT pathway [ 75 ], is an AR mechanism against osimertinib in PC9 and HCC827 cells, and that osimertinib plus an ACK1 inhibitor ([R]-9b) might overcome osimertinib resistance [ 48 ]. In addition, many groups have suggested that the RAS–RAF–MEK–ERK pathway is involved in the acquisition of resistance to first-line osimertinib in vitro.…”

Section: Cell Line Models Used To Analyze Resistance Mechanisms Tomentioning

confidence: 99%

“… Scheme of the signal pathway and molecules that reportedly cause osimertinib resistance—AXL [ 39 , 41 , 52 ], HER3 [ 45 ], IGF1R [ 51 , 57 ], MET [ 33 , 52 ], TGFβ1 [ 40 ], TGFβ2 [ 59 ], BRAF [ 43 ], RAS [ 32 , 35 ], ERK [ 37 ], Src-AKT [ 35 ], ACK1 [ 48 ], CDK4/6 [ 55 ], BCL-2 [ 56 ], MCL-1 [ 34 ], BIM [ 34 , 50 ], YAP [ 54 ], ANKRD1 [ 36 ], microRNA-200c [ 46 ], ZEB1 [ 46 , 58 ], and IRE1α [ 38 ] (highlighted in red)—in cell line models treated with osimertinib. EGFR, epidermal growth factor receptor; AXL, AXL receptor tyrosine kinase; ERBB3, human epidermal growth factor receptor-3; IGF1R, insulin-like growth factor-1 receptor; MET, MET proto-oncogene, receptor tyrosine kinase; TGF, transforming growth factor; ACK1, activated Cdc42-associated kinase-1; CDK4/6, cyclin-dependent kinase; BCL-2, B-cell lymphoma-2; YAP, yes-associated protein; ANKRD1, ankyrin repeat domain-1; IRE1α, inositol-requiring enzyme-1α.…”

Section: Figurementioning

confidence: 99%

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Cell Line Models for Acquired Resistance to First-Line Osimertinib in Lung Cancers—Applications and Limitations

Ohara

Suda

Mitsudomi

2021

Cells

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are first-line drugs for lung cancers with activating EGFR mutations. Although first- and second-generation EGFR-TKIs were standard first-line treatments, acquired resistance (AR) to these drugs is almost inevitable. Cell line models have been widely used to explore the molecular mechanisms of AR to first- and second-generation EGFR-TKIs. Many research groups, including ours, have established AR cell lines that harbor the EGFR T790M secondary mutation, MET gene amplification, or epithelial–mesenchymal transition (EMT) features, which are all found in clinical specimens obtained from TKI-refractory lesions. Currently, many oncologists prescribe osimertinib, a third-generation EGFR-TKI that can overcome T790M-mediated resistance, as a first-line TKI. Although few clinical data are available about AR mechanisms that arise when osimertinib is used as a first-line therapy, many research groups have established cell lines with AR to osimertinib and have reported on their AR mechanisms. In this review, we summarize the findings on AR mechanisms against first-line osimertinib obtained from analyses of cell line models.

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Section: Search Criteria For Published Studiesmentioning

confidence: 99%

Section: Cell Line Models Used To Analyze Resistance Mechanisms Tomentioning

confidence: 99%

Section: Cell Line Models Used To Analyze Resistance Mechanisms Tomentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Cell Line Models for Acquired Resistance to First-Line Osimertinib in Lung Cancers—Applications and Limitations

Ohara

Suda

Mitsudomi

2021

Cells

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“…Nonsmall‐cell lung cancer (NSCLC) is the most frequent type of lung cancer 1 . The worldwide incidence of NSCLC is increasing each year; in 2018, an estimated 2 million new cases of lung cancer worldwide were reported 2 .…”

Section: Introductionmentioning

confidence: 99%

Silencing of lncRNA CRNDE attenuates nonsmall‐cell lung cancer progression by mediating the miR‐455‐3p/HDAC2 axis

Chen

Zeng

et al. 2022

The Kaohsiung J of Med Scie

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Nonsmall‐cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR‐455‐3p, and HDAC2 was explored by dual‐luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR‐455‐3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)‐mutant NSCLC cells. Moreover, inhibition of miR‐455‐3p exhibited the opposite effect. CRNDE bound with miR‐455‐3p, and HDAC2 was found to be targeted by miR‐455‐3p. Meanwhile, miR‐455‐3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR‐455‐3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR‐455‐3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.

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The Role of miR-29a and miR-143 on the Anti-apoptotic MCL-1/cIAP-2 Genes Expression in EGFR Mutated Non-small Cell Lung Carcinoma Patients

Abrehdari-Tafreshi,

Arefian,

Rakhshani

et al. 2024

Biochem Genet

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Inhibition of ACK1 delays and overcomes acquired resistance of EGFR mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib

Cited by 15 publications

References 28 publications

Cell Line Models for Acquired Resistance to First-Line Osimertinib in Lung Cancers—Applications and Limitations

Cell Line Models for Acquired Resistance to First-Line Osimertinib in Lung Cancers—Applications and Limitations

Silencing of lncRNA CRNDE attenuates nonsmall‐cell lung cancer progression by mediating the miR‐455‐3p/HDAC2 axis

The Role of miR-29a and miR-143 on the Anti-apoptotic MCL-1/cIAP-2 Genes Expression in EGFR Mutated Non-small Cell Lung Carcinoma Patients

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