Signal Transduction Pathways in Breast Cancer – Drug Targets and Challenges

Azab, Samar S.; Al-Hendy, Ayman

doi:10.5772/23855

Cited by 4 publications

(4 citation statements)

References 191 publications

(216 reference statements)

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“…Disrupted signaling pathways are generally associated with the development of many types of cancers [35,36], indicating that these signaling pathways can be promising therapeutic targets for cancer therapy and drug development. Among such pathways, aberrantly activated STAT3 signaling is considered an attractive therapeutic target for the treatment of many types of human diseases, including cancer [37,38].…”

Section: Discussionmentioning

confidence: 99%

Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

Kim

Lee

Song

et al. 2019

JCM

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Persistently activated STAT3 is a promising target for a new class of anticancer drug development and cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 inhibitor and may be a promising agent for the development of anticancer drugs.

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Section: Discussionmentioning

confidence: 99%

Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

Kim

Lee

Song

et al. 2019

JCM

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“…Targeted therapeutic approaches focus on proteins and pathways such as MAPK, HER2/EKBB2, p13K/Akt/mTOR, PAPP, TGF-α, EGF, and p53 identified in the malignancy. 5,6 Terlikowska et al 7 have identified approximately twenty-six curcumin mediated signalling pathways such as PPAR, COX-2, EGFR and NF-κB. In vivo studies are often performed in three established adenocarcinoma and invasive ductal carcinoma cell lines; MDA-MB-231, MDA-MB-468, SkBr3 and MDA-MB-435, MCF-7, T47D respectively.…”

Section: Introductionmentioning

confidence: 99%

Recent advances of curcumin and its analogues in breast cancer prevention and treatment

2015

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More than 230,000 diagnosed cases of invasive breast cancer in women was estimated in 2014 and an expected 40,000 deaths attributed to the aggressive carcinoma. An effective approach to diminish the morbidity and mortality of breast cancer is the development of chemopreventive and chemotherapeutic agents. Nutraceuticals have demonstrated their ability to proficiently halt carcinogenesis. The administration of natural compounds able to effectively serve as chemoprevention and chemotherapeutics without causing harm or adverse effects is imperative. Curcumin derived from the rhizome of Curcuma longa L., is a common spice of India, used for centuries because of its medicinal properties. The main component of curcumin possesses a wide range of biological activities; anti-proliferative, anti-inflammatory, and apoptotic characteristics modulated through the inactivation of pathways such as EGK and Akt/mTOR. In addition, curcumin alters the expression of cytokines, transcription factors, and enzymes involved in cell vitality. The in vivo application of curcumin in breast cancer is hindered by its limited bioavailabiity. The synthesis of curcumin analogues and delivery via nanoparticles has demonstrated enhanced bioavailability of curcumin in the malignancy. This review focuses on recent developments in the use of curcumin, curcumin analogues, and novel delivery systems as a preventive and therapeutic method for breast cancer.

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“…70,71 Gene and protein expression studies were conducted to investigate the involvement of the PTEN-PI3K/AKT pathway in breast cancer cells treated with TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs in the presence of 5-ALA, as shown in Figures 7 and 8. 72,73 For this purpose, IC 50 concentrations of TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs were treated for 24 h, followed by the semiquantitative RT-PCR analysis of PTEN, PI3K, and AKT mRNA expression levels. Figure 7a− c shows the upregulation of PTEN in breast cancer cells (MCF-7 and MDA-MB-231) in the presence of TPP-CTAB@ GNRs and TPP-PSS-CTAB@GNRs.…”

Section: Resultsmentioning

confidence: 99%

Impact of Surface Charge-Tailored Gold Nanorods for Selective Targeting of Mitochondria in Breast Cancer Cells Using Photodynamic Therapy

Vinita,

Devan,

Durgadevi

et al. 2023

ACS Omega

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Herein, the impact of surface charge tailored of gold nanorods (GNRs) on breast cancer cells (MCF-7 and MDA-MB-231) upon conjugation with triphenylphosphonium (TPP) for improved photodynamic therapy (PDT) targeting mitochondria was studied. The salient features of the study are as follows: (i) positive (CTAB@GNRs) and negative (PSS-CTAB@GNRs) surface-charged gold nanorods were developed and characterized; (ii) the mitochondrial targeting efficiency of gold nanorods was improved by conjugating TPP molecules; (iii) the conjugated nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) were evaluated for PDT in the presence of photosensitizer (PS), 5-aminolevulinic acid (5-ALA) in breast cancer cells; (iv) both nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) induce apoptosis, damage DNA, generate reactive oxygen species, and decrease mitochondrial membrane potential upon 5-ALA-based PDT; and (v) 5-ALA-PDT of two nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) impact cell signaling (PI3K/AKT) pathway by upregulating proapoptotic genes and proteins. Based on the results, we confirm that the positively charged (rapid) nanoprobes are more advantageous than their negatively (slow) charged nanoprobes. However, depending on the kind and degree of cancer, both nanoprobes can serve as efficient agents for delivering anticancer therapy.

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Signal Transduction Pathways in Breast Cancer – Drug Targets and Challenges

Cited by 4 publications

References 191 publications

Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

Recent advances of curcumin and its analogues in breast cancer prevention and treatment

Impact of Surface Charge-Tailored Gold Nanorods for Selective Targeting of Mitochondria in Breast Cancer Cells Using Photodynamic Therapy

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