Literature DB >> 27931828

Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data.

Loay Kassem1, Omar Abdel-Rahman2.   

Abstract

BACKGROUND: mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers.
METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results.
RESULTS: A total of 23 studies including 980 patients were considered eligible for our review. Our review included 16 phase II and 7 phase I studies with the majority of patients having uterine cancers. Regarding Endometrial cancer, the CBR ranged from 21% to 60% and median PFS from 2.8 months to 7.3 months. In Ovarian cancers, CBR ranged from 24% to 50% and median PFS from 3.2 months to 5.9 months. In the single phase II study in cervical cancer the CBR was 61% and median PFS was 3.5 months. The toxicity profile was consistent with what was observed previously in other malignancies with fatigue, mucositis, and hematological toxicities being the most common adverse events observed.
CONCLUSION: mTOR inhibitors seem to be a promising option in the second line management of advanced gynecological cancers with best safety and efficacy outcomes when given as a single agent or in combination with hormonal treatment. More research is needed for better patient selection. Copyright Â
© 2016 Elsevier Ireland Ltd. All rights reserved.

Entities:  

Keywords:  Cervical cancer; Endometrial cancer; Everolimus; Ovarian cancer; Temsirolimus

Mesh:

Substances:

Year:  2016        PMID: 27931828     DOI: 10.1016/j.critrevonc.2016.10.003

Source DB:  PubMed          Journal:  Crit Rev Oncol Hematol        ISSN: 1040-8428            Impact factor:   6.312


  8 in total

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Journal:  Biochim Biophys Acta Biomembr       Date:  2017-04-25       Impact factor: 3.747

2.  Nuclear receptor 4A1 (NR4A1) antagonists induce ROS-dependent inhibition of mTOR signaling in endometrial cancer.

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Review 4.  Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors.

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7.  miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development.

Authors:  Jian Ma; Da Li; Fan-Fei Kong; Di Yang; Hui Yang; Xiao-Xin Ma
Journal:  J Exp Clin Cancer Res       Date:  2018-02-01

8.  Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-BclxL strategies through Mcl-1 down-regulation.

Authors:  Marie-Laure Bonnefond; Romane Florent; Sophie Lenoir; Bernard Lambert; Edwige Abeilard; Florence Giffard; Marie-Hélène Louis; Nicolas Elie; Mélanie Briand; Denis Vivien; Laurent Poulain; Pascal Gauduchon; Monique N'Diaye
Journal:  Oncotarget       Date:  2018-09-21
  8 in total

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