Targeted Therapies in Epithelial Ovarian Cancer

Medel, Nicanor I. Barrena; Wright, Jason D.; Herzog, Thomas J.

doi:10.1155/2010/314326

Cited by 16 publications

(18 citation statements)

References 50 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, further clinical studies are needed to show that DIM has no side effects. Considering the fact that several EGFR-targeted therapies such as monoclonal antibodies, small molecule inhibitors, or receptor tyrosine kinase inhibitors failed to pass phase II clinical trials to treat ovarian cancer (Barrena Medel et al, 2010), it is tempting to speculate that DIM should be tried in clinical trials as a therapeutic option against ovarian cancer based on the success of DIM in other cancer models.…”

Section: Discussionmentioning

confidence: 99%

Blocking Epidermal Growth Factor Receptor Activation by 3,3′-Diindolylmethane Suppresses Ovarian Tumor Growth In Vitro and In Vivo

Kandala¹,

Wright²,

Srivastava

2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Genetic alterations, including the overexpression of epidermal growth factor receptor (EGFR) (in approximately 70% of ovarian tumors), play a crucial role in the signal transduction pathways that regulate key cellular functions, such as cell survival and proliferation, and are responsible for compromising traditional chemotherapy. 3,3Ј-Diindolylmethane (DIM) is an indole compound present in Brassica vegetables. In our previous studies, we demonstrated that BR-DIM, a formulated version of DIM, suppressed the growth of ovarian cancer cells by causing cell cycle arrest and apoptosis. In the present study, we delineated the mechanism by which DIM suppressed the growth of SKOV-3, OVCAR-3, and TOV-21G human ovarian cancer cells. DIM treatment caused significant down-regulation of the constitutive EGFR protein level as well as phosphorylation of EGFR at Tyr1068, Tyr992, Tyr845, and Tyr1173 in various ovarian cancer cells. To determine whether DIM suppressed the activation of EGFR by activating phosphorylation, cells were treated with epidermal growth factor. Epidermal growth factor treatment significantly blocked the DIM-mediated inhibition of EGFR activation and apoptosis in both SKOV-3 and OVCAR-3 cells. In addition, DIM treatment drastically reduced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK), which are downstream to EGFR, without affecting their protein levels. DIM treatment also inhibited the kinase activity of ERK, as observed by the down-regulation of phospho-E twenty-six like transcription factor 1 (p-ELK1) in all three ovarian cancer cell lines. DIM significantly suppressed the growth of ovarian tumors in vivo. Tumor growth suppressive effects of DIM in SKOV-3 tumor xenografts were associated with reduced phosphorylation of EGFR, MEK, and ERK. These results indicate that DIM induces apoptosis in ovarian cancer cells by inhibiting the EGFR-ERK pathway in vitro and in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Blocking Epidermal Growth Factor Receptor Activation by 3,3′-Diindolylmethane Suppresses Ovarian Tumor Growth In Vitro and In Vivo

Kandala¹,

Wright²,

Srivastava

2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…The high rates of acquired chemoresistance in this disease underscore the need to develop targeted therapies, where patient selection can be based upon well-characterized biomarkers [3]. To date, the most successful approach incorporating biologic therapy for this disease has been through drugs that target the vascular growth factor (VEGF) pathway, although the improvement in progression-free survival (PFS) is underwhelming [4, 5].…”

Section: Introductionmentioning

confidence: 99%

High Incidence of ErbB3, ErbB4, and MET Expression in Ovarian Cancer

Davies

Holmes

Lomo

et al. 2014

International Journal of Gynecological Pathology

View full text Add to dashboard Cite

“…The standard treatment of advanced ovarian cancer is cytoreductive surgery followed by a combination platinum-based chemotherapy [1]. Cisplatin is one of the most effective cell cycle non-specific drugs for the treatment of ovarian cancer, and the mechanism involved in the process of its cytotoxicity includes survival inhibition and apoptosis [2].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-130a contributes to cisplatin resistance in ovarian cancer cells by targeting X-linked inhibitor of apoptosis (XIAP) directly

Zhang¹,

Huang²,

Zhao³

et al. 2013

ABBS

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are short, highly conserved small non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes. Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells to chemotherapeutic agents. To investigate the possible role of miR-130a in the development of cisplatin resistance in human ovarian cancer cell line A2780, we evaluated the expression of microRNA-130a (miR-130a) in the cells by the quantitative real-time reverse transcriptionpolymerase chain reaction. The results showed that miR130a was significantly down-regulated in cisplatin-resistant ovarian cancer cells. MTT assay and flow cytometry (FCM) results showed that over-expression of miR-130a regulated apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cancer cells. Furthermore, we found that miR-130a can directly target XIAP, and participate in the regulation of apoptosis. The up-regulation of miR-130a led to a significant decrease in the XIAP mRNA levels and protein levels. XIAP plays an important role in cisplatin resistance in ovarian cancer cell line A2780. Our findings suggested that miR-130a could play a role in the development of cisplatin resistance in ovarian cancer cell line A2780, at least in part by modulation of apoptosis via targeting XIAP.

show abstract

Targeted Therapies in Epithelial Ovarian Cancer

Cited by 16 publications

References 50 publications

Blocking Epidermal Growth Factor Receptor Activation by 3,3′-Diindolylmethane Suppresses Ovarian Tumor Growth In Vitro and In Vivo

Blocking Epidermal Growth Factor Receptor Activation by 3,3′-Diindolylmethane Suppresses Ovarian Tumor Growth In Vitro and In Vivo

High Incidence of ErbB3, ErbB4, and MET Expression in Ovarian Cancer

Downregulation of miR-130a contributes to cisplatin resistance in ovarian cancer cells by targeting X-linked inhibitor of apoptosis (XIAP) directly

Contact Info

Product

Resources

About