Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

Davis, Nicole M.; Sokolosky, Melissa L.; Stadelman, Kristin M.; Abrams, Stephen L.; Libra, Massimo; Candido, Saverio; Nicoletti, Ferdinando; Polesel, Jerry; Maestro, Roberta; D’Assoro, Antonino B.; Drobot, L. B.; Rakus, Dariusz; Gizak, Agnieszka; Laidler, Piotr; Dulińska-Litewka, Joanna; Bäsecke, Jörg; Mijatović, Sanja; Maksimović‐Ivanić, Danijela; Montalto, Giuseppe; Cervello, Melchiorre; Fitzgerald, Timothy L.; Demidenko, Zoya N.; Martelli, Alberto M.; Cocco, Lucio; Steelman, Linda S.; McCubrey, James A.

doi:10.18632/oncotarget.2209

Cited by 217 publications

(167 citation statements)

References 314 publications

(279 reference statements)

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“…Activated EGFR stimulates a number of downstream signaling molecules, leading to the activation of various major pathways which are essential to tumor growth, progression, prevention of apoptosis, drug resistance, and metastasis. [26][27][28] According to their functions, the main downstream pathway molecules of activated EGFR can be activated through kinase-dependent reaction, such as PI3K, K-Ras, and Raf-1, or through its ability to physically interact with other proteins (kinase-independent), such as Akt and MAPK. 25 As top-line molecules of EGFR/PI3K/Akt/mTOR pathway, the expressions of EGFR, PI3K, and Akt detected in the cell lysates were repressed by the treatment of MYR (Figures 4 and 7).…”

Section: Discussionmentioning

confidence: 99%

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

Tang

Huang

Gui

et al. 2016

IJN

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As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells.

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Section: Discussionmentioning

confidence: 99%

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

Tang

Huang

Gui

et al. 2016

IJN

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“…Indeed, concurrent perturbations of the PI3K/AKT/mTOR and the mitogenactivated protein kinase (MAPK) cascades are frequently Targeting Oncogenic Pathways in Breast Cancer observed in tumors. Several inhibitors of the Raf/MEK/ERK pathway are currently under clinical evaluation alone and in combination with PIK3CA/mTOR inhibitors (Table 3) [9,58,94,95]. Furthermore, PI3K inhibition has been shown to boost the ERK pathway through the enhancement of the epidermal growth factor receptor (EGFR)/HER2/human epidermal growth factor receptor 3 (HER3) signaling, and HER3 may in turn promote the reactivation of the PI3K/AKT and MAPK pathways [96,97].The modest activity of EGFR inhibitors in TNBC may also be due to crosstalk between signaling pathways and compensatory feedback loops [98][99][100][101].…”

Section: Potential New Therapeutic Targets and Treatment Strategies Dmentioning

confidence: 99%

Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer

et al. 2016

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Advances in DNA and RNA sequencing revealed substantially greater genomic complexity in breast cancer than simple models of a few driver mutations would suggest. Only very few, recurrent mutations or copy-number variations in cancer-causing genes have been identified. The two most common alterations in breast cancer are TP53 (affecting the majority of triple-negative breast cancers) and PIK3CA (affecting almost half of estrogen receptor-positive cancers) mutations, followed by a long tail of individually rare mutations affecting <1%–20% of cases. Each cancer harbors from a few dozen to a few hundred potentially high-functional impact somatic variants, along with a much larger number of potentially high-functional impact germline variants. It is likely that it is the combined effect of all genomic variations that drives the clinical behavior of a given cancer. Furthermore, entirely new classes of oncogenic events are being discovered in the noncoding areas of the genome and in noncoding RNA species driven by errors in RNA editing. In light of this complexity, it is not unexpected that, with the exception of HER2 amplification, no robust molecular predictors of benefit from targeted therapies have been identified. In this review, we summarize the current genomic portrait of breast cancer, focusing on genetic aberrations that are actively being targeted with investigational drugs.

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“…Breast cancer is not gender specific [6] [7]. The frequency of breast cancer in men is approximately 100-fold lower than in women [8]. In another study, it was estimated that there are approximately 2.5 million survivors of breast cancer that are present in the USA [9].…”

Section: Introductionmentioning

confidence: 99%

Awareness about Early Detection Methods, Symptoms and Risk Factors towards Breast and Cervical Cancer among the Female Students of Mawlana Bhashani Science and Technology University (MBSTU), Santosh, Tangail, Bangladesh

Zohora¹,

Paul²,

Mahmud³

et al. 2017

ABCR

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The study was conducted to ensure knowledge, attitude, awareness about breast and cervical cancer among the female students of Mawlana Bhashani Science and Technology University. This study was carried out from July to September, 2015 among the participants of university female halls, different female hostels and different faculty of the university by using a validated questionnaire which was developed for this study. A total 250 female students, at the age of (18 -26) years were participated. Collected information was analyzed using SPSS, Graph-pad Prism and MS Excel. The results showed that about 87.6% participants were undergraduate. Most of them come from village (45.6%) and city (36.0%). About 90% were Muslims and the socioeconomic level of most of the participants was middle (90.4%). In case of food intake patterns, it was observed that 35.6% participants eat chips, soft drinks, popcorn everyday; 40.4% eat meat regularly; 24% eat sugar everyday; 27.6% eat fruits and vegetables every day. Among them, 55.6% girls maintained daily 1 hour physical activity; 37.2% did exercise rarely; 34.8% participants rarely do strenuous exercise. About 84.4% respondents have not any family history of cancer; 6% participants have sister or mother having breast tumor and 7.2% have at least more than one close relative who have cancer. Among the participants, only 0.8% drank alcohol; 1.2% have addiction of smoking cigarette; 15.6% girls wear tight bra; 3.6% have benign breast disease and 2.8% participants have attended in breast or cervical cancer screening programs. The 50moderate numbers of girls have breast cancer screening practice. Among them, only 28.8% participants have ever heard about BSE (Breast self-examination) and 40.4% have not any knowledge about breast cancer treatment. About 50.8% respondents don't have any knowledge about cervical cancer treatment. The village people are the most risky group. About 17.02% girls recognized weakened immune system as a risk factor of cervical cancer. It can be concluded that, knowledge of participants regarding breast and cervical cancer is poor. Targeted education should be implemented to improve the knowledge of respondents about early detection methods and symptoms of breast and cervical cancer.

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Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

Cited by 217 publications

References 314 publications

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer

Awareness about Early Detection Methods, Symptoms and Risk Factors towards Breast and Cervical Cancer among the Female Students of Mawlana Bhashani Science and Technology University (MBSTU), Santosh, Tangail, Bangladesh

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