Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors

Highlights ► Combination of mTOR inhibitors with Topoisomerase II inhibitors. ► Combination is synergistic in head and neck and breast cancer cells. ► mTOR inhibitor sensitizes adriamycin/cisplatin resistant cells. ► DNA repair is required after induction of DNA damage by topoisomerase II inhibitors...

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Bibliographic Details
Published in:Cancer letters 2011-12, Vol.311 (1), p.20-28
Main Authors: Gaur, Shikha, Chen, Linling, Yang, Lixin, Wu, Xiwei, Un, Frank, Yen, Yun
Format: Article
Language:English
Subjects:
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Apoptosis
Apoptosis - drug effects
Autophagy
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer therapies
carcinoma
Cell cycle
Cell Cycle - drug effects
Cell growth
Cell Line, Tumor
cell proliferation
Chemotherapeutic drugs
Chemotherapy
chromatin
cisplatin
Cisplatin - administration & dosage
Cloning
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair
DNA topoisomerase (ATP-hydrolysing)
DNA Topoisomerases, Type II - metabolism
doxorubicin
Doxorubicin - administration & dosage
Drug dosages
Drug resistance
Drug Resistance, Neoplasm
Drug Synergism
Eukaryotic Initiation Factors - metabolism
Everolimus
Female
G2/M arrest
Head & neck cancer
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - enzymology
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - pathology
Hematology, Oncology and Palliative Medicine
Humans
Kinases
mTOR
multiple drug resistance
Phosphorylation
Phosphorylation - drug effects
Proteins
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Sirolimus - administration & dosage
Sirolimus - analogs & derivatives
Topoisomerase II
Topoisomerase II Inhibitors - administration & dosage
Topoisomerase II Inhibitors - pharmacology
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
Tumors
γH2AX
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Summary:Highlights ► Combination of mTOR inhibitors with Topoisomerase II inhibitors. ► Combination is synergistic in head and neck and breast cancer cells. ► mTOR inhibitor sensitizes adriamycin/cisplatin resistant cells. ► DNA repair is required after induction of DNA damage by topoisomerase II inhibitors. ► mTOR inhibitor restores chemosensitivity by blocking the translation of proteins.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.06.005