The Activity of Trabectedin As a Single Agent or in Combination with Everolimus for Clear Cell Carcinoma of the Ovary

Mabuchi, Seiji; Hisamatsu, Takeshi; Kawase, Chiaki; Hayashi, Masami; Sawada, Kenjirou; Mimura, Kazuya; Takahashi, Kazuhiro; Takahashi, Toshifumi; Kurachi, Hirohisa; Kimura, Tadashi

doi:10.1158/1078-0432.ccr-10-2987

Cited by 35 publications

(45 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another potential avenue is the combination of targeted agents with effective cytotoxic agents, as targeting agents are generally cytostatic. Intriguing preclinical results suggest that trabectedin is the most effective of the existing cytotoxic agents against CCC, 37 and this may be enhanced by the addition of an mTOR inhibitor. This combination warrants further investigation in future clinical studies.…”

Section: Future Directionsmentioning

confidence: 99%

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary

Okamoto

Glasspool

Mabuchi

et al. 2014

Int J Gynecol Cancer

Self Cite

132

View full text Add to dashboard Cite

Clear cell carcinoma of the ovary (CCC) is a histologic subtype of epithelial ovarian cancer with a distinct clinical behavior. There are marked geographic differences in the prevalence of CCC. The CCC is more likely to be detected at an early stage than high-grade serous cancers, and when confined within the ovary, the prognosis is good. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. Cytoreductive surgery should be performed for patients with stage II, III, or IV disease. An international phase III study to compare irinotecan/cisplatin and paclitaxel/carboplatin as adjuvant chemotherapy for stage IIV CCC has completed enrollment (GCIG/JGOG3017). Considering the frequent PIK3CA mutation in CCC, dual inhibitors targeting PI3K, AKT in the mTOR pathway, are promising. Performing these trials and generating the evidence will require considerable international collaboration.

show abstract

Section: Future Directionsmentioning

confidence: 99%

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary

Okamoto

Glasspool

Mabuchi

et al. 2014

Int J Gynecol Cancer

Self Cite

132

View full text Add to dashboard Cite

show abstract

“…The authors concluded that Trabectedin/PLD combination improved progression-free survival and overall response rate in patients displaying a platinum-free interval of more than 6 months, compared with patients receiving PLD alone (35,36). In a more recent preclinical study, it was shown that Trabectedin inhibited tumor growth in xenograft models of clear cell carcinoma of the ovary, which further shows its potential as either a first-line or second-line therapy for certain subgroups of ovarian neoplasms (37). As such, patients exhibiting high amounts of immune infiltration in tumors may benefit from agents targeting activated TAMs.…”

Section: Tumor-associated Macrophagesmentioning

confidence: 99%

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

Musrap

Diamandis

2012

Molecular Cancer Research

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in North American women. Given that EOC encompasses a broad class of tumors consisting of a variety of different histologic and molecular subtypes, which generates genetically and etiologically distinct tumors, several challenges arise during treatment of patients with this disease. Overlaying this complexity is the contribution of supporting cells, particularly stromal components such as fibroblasts and immune infiltrates that collectively create a microenvironment that promotes and enhances cancer progression. A notable example is the induction of angiogenesis, which occurs through the secretion of pro-angiogenic factors by both tumor and tumor-associated cells. The recent development of angiogenic inhibitors targeting tumor vasculature, which have been shown to improve patient outcome when combined with standard therapy, has launched a paradigm shift on how cancer patients should be treated. It is evident that future clinical practices will focus on the incorporation of therapies that antagonize the protumoral effects of such microenvironment contributors. Herein, an overview of the varying tumor-host interactions that influence tumor behavior will be discussed, in addition to the recent efforts undertaken to target these interactions and their potential to revolutionize EOC patient care.

show abstract

“…Cisplatin activates the mTOR survival pathway in epithelial and clear-cell carcinoma ovarian cancer cells, which may counteract cisplatin-induced apoptosis and in turn lead to cisplatin resistance (14,15). The mTOR inhibitors, rapamycin and its analogs, including everolimus, efficiently enhance the therapeutic efficacy of platinum in clear-cell ovarian carcinoma cells (16,17). Therefore, mTOR is a promising therapeutic target for the treatment of ovarian cancer when combined with cisplatin.…”

Section: Introductionmentioning

confidence: 99%

Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer

et al. 2018

View full text Add to dashboard Cite

Abstract. The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic target in various cancer cells. mTOR activation decreases the sensitivity of ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various cancer cells by mTOR suppression. The present study examined whether cardamonin combined with cisplatin is efficacious for the anti-proliferation of ovarian cancer cells. The anti-proliferative effect was determined by MTT and cell cycle assays. Activation of the mTOR signal pathway and the expression of anti-apoptotic proteins were evaluated by western blot analysis. Cardamonin significantly enhanced the effects of cisplatin on cell proliferation and cell cycle progression. The expression of B cell lymphoma-2, X-linked inhibitor of apoptosis protein and Survivin was significantly decreased following combination treatment. Furthermore, the activation of mTOR and its downstream 70 kDa ribosomal protein S6 kinase was inhibited by cardamonin. These results demonstrated that the combinatorial effects of cardamonin and cisplatin on anti-proliferation were enhanced by suppressing the expression of anti-apoptotic proteins and activation of mTOR in ovarian cancer cells.

show abstract

The Activity of Trabectedin As a Single Agent or in Combination with Everolimus for Clear Cell Carcinoma of the Ovary

Cited by 35 publications

References 36 publications

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer

Contact Info

Product

Resources

About