Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models

Belli, Valentina; Matrone, Nunzia; Napolitano, Stefania; Migliardi, Giorgia; Cottino, Francesca; Bertotti, Andrea; Trusolino, Livio; Martinelli, Erika; Morgillo, Floriana; Ciardiello, Davide; Falco, Vincenzo De; Giunta, Emilio Francesco; Bracale, Umberto; Ciardiello, Fortunato; Troiani, Teresa

doi:10.1186/s13046-019-1230-z

Cited by 20 publications

(15 citation statements)

References 45 publications

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“…Then, the hub lncRNAs function was evaluated by GO and KEGG analyses. The results demonstrated that the MAPK signaling pathway and protein biological regulation were the most relevant functional, which was consistent with previous studies (Belli et al, 2019 ; Schumacher et al, 2019 ; Vitiello et al, 2019 ).…”

Section: Discussionsupporting

confidence: 92%

Identification of LncRNAs Associated With FOLFOX Chemoresistance in mCRC and Construction of a Predictive Model

Zhang

Sun

et al. 2021

Front. Cell Dev. Biol.

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Oxaliplatin, fluorouracil plus leucovorin (FOLFOX) regimen is the first-line chemotherapy of patients with metastatic colorectal cancer (mCRC). However, studies are limited regarding long non-coding RNAs (lncRNAs) associated with FOLFOX chemotherapy response and prognosis. This study aimed to identify lncRNAs associated with FOLFOX chemotherapy response and prognosis in mCRC patients and to construct a predictive model. We analyzed lncRNA expression in 11 mCRC patients treated with FOLFOX chemotherapy before surgery (four sensitive, seven resistant) by Gene Array Chip. The top eight lncRNAs (AC007193.8, CTD-2008N3.1, FLJ36777, RP11-509J21.4, RP3-508I15.20, LOC100130950, RP5-1042K10.13, and LINC00476) for chemotherapy response were identified according to weighted correlation network analysis (WGCNA). A competitive endogenous RNA (ceRNA) network was then constructed. The crucial functions of the eight lncRNAs enriched in chemotherapy resistance were mitogen-activated protein kinase (MAPK) and proteoglycans signaling pathway. Receiver operating characteristic (ROC) analysis demonstrated that the eight lncRNAs were potent predictors for chemotherapy resistance of mCRC patients. To further identify a signature model lncRNA chemotherapy response and prognosis, the validation set consisted of 196 CRC patients from our center was used to validate lncRNAs expression and prognosis by quantitative PCR (qPCR). The expression of the eight lncRNAs expression between CRC cancerous and adjacent non-cancerous tissues was also verified in the validation data set to determine the prognostic value. A generalized linear model was established to predict the probability of chemotherapy resistance and survival. Our findings showed that the eight-lncRNA signature may be a novel biomarker for the prediction of FOLFOX chemotherapy response and prognosis of mCRC patients.

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Section: Discussionsupporting

confidence: 92%

Identification of LncRNAs Associated With FOLFOX Chemoresistance in mCRC and Construction of a Predictive Model

Zhang

Sun

et al. 2021

Front. Cell Dev. Biol.

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“…With the aim of getting a better understanding of the mechanisms of resistance to HER2-directed and EGFR-directed therapies, it has been recently reported that increased expression of MUC1 and MET , decreased expression of PTEN , and an activating mutation in PIK3CA is accompanied with HER2 -amplified in mCRC. These findings strongly highlight the molecular heterogeneity of the resistance to anti-EGFR therapy [39,46,49,50,51,52].…”

Section: Acquired Resistance To Anti-egfr Treatment In Crc Patientsmentioning

confidence: 88%

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Giordano

Remo²,

Porrás

et al. 2019

Cancers

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: Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy in patients with RAS wild type metastatic colorectal cancer (mCRC) has revolutionized the treatment of CRC, but with less results than initially envisaged. In recent years, the discovery of multiple pathways leading to the escape from anti-EGFR therapy has revealed an enormous complexity and heterogeneity of human CRC due to the intrinsic genomic instability and immune/cancer cell interaction. Therefore, understanding the mechanistic basis of acquired resistance to targeted therapies represents a major challenge to improve the clinical outcomes of patients with CRC. The latest findings strongly suggest that complex molecular alterations coupled with changes of the immune tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonist. In this review, we discuss the most recent findings that contribute to both primary and acquired anti-EGFR therapy resistance. In addition, we analyze how strategies aiming to enhance the favorable effects in the tumor microenvironment may contribute to overcome resistance to EGFR therapies.

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“…These phenomena result from different cell signalization pathways in the form of a downstream of phosphorylations/dephosphorylations through the epithelial cell when the HER2 receptor is activated. The phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT) [23] and the RAF/MEK/MAPK pathways are the most solicited [24]. The detection of HER2 in particular is very relevant because breast cancers involving HER2 protein overexpression, also known as HER2-positive (HER2+) breast cancer, tend to be more aggressive with a more rapid progression and a higher propensity to come back in comparison with HER2-negative (HER2-) ones [25].…”

Section: Introductionmentioning

confidence: 99%

HER2 biosensing through SPR-envelope tracking in plasmonic optical fiber gratings

Lobry¹,

Loyez²,

Chah³

et al. 2020

Biomed. Opt. Express

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In the biomedical detection context, plasmonic tilted fiber Bragg gratings (TFBGs) have been demonstrated to be a very accurate and sensitive sensing tool, especially well-adapted for biochemical detection. In this work, we have developed an aptasensor following a triple strategy to improve the overall sensing performances and robustness. Single polarization fiber (SPF) is used as biosensor substrate while the demodulation is based on tracking a peculiar feature of the lower envelope of the cladding mode resonances spectrum. This method is highly sensitive and yields wavelength shifts several tens of times higher than the ones reported so far based on the tracking of individual modes of the spectrum. An amplification of the response is further performed through a sandwich assay by the use of specific antibodies. These improvements have been achieved on a biosensor developed for the detection of the HER2 (Human Epidermal Growth Factor Receptor-2) protein, a relevant breast cancer biomarker. These advanced developments can be very interesting for point-of-care biomedical measurements in a convenient practical way.

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Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models

Cited by 20 publications

References 45 publications

Identification of LncRNAs Associated With FOLFOX Chemoresistance in mCRC and Construction of a Predictive Model

Identification of LncRNAs Associated With FOLFOX Chemoresistance in mCRC and Construction of a Predictive Model

Immune Resistance and EGFR Antagonists in Colorectal Cancer

HER2 biosensing through SPR-envelope tracking in plasmonic optical fiber gratings

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