PMID- 24097108
OWN - NLM
STAT- MEDLINE
DCOM- 20140616
LR  - 20211203
IS  - 1531-703X (Electronic)
IS  - 1040-8746 (Linking)
VI  - 25
IP  - 6
DP  - 2013 Nov
TI  - New strategies to overcome resistance to mammalian target of rapamycin inhibitors 
      in breast cancer.
PG  - 587-93
LID - 10.1097/CCO.0000000000000014 [doi]
AB  - PURPOSE OF REVIEW: To review the studies addressing mammalian target of rapamycin 
      (mTOR) inhibitors in breast cancer and resistance to rapalogs. Preclinical and 
      clinical studies have suggested mTOR inhibitors may help overcome the resistance 
      to endocrine therapy and trastuzumab. Despite much interest, knowledge of the 
      mechanism and molecular response to mTOR inhibitors is incomplete. RECENT 
      FINDINGS: Resistance to mTOR inhibitors has been explored in preclinical studies 
      and can be defined as primary, associated with amplifications or mutations of 
      different kinases, or secondary, in which rapalog activates the feedback loops 
      involving the insulin-like growth factor I receptor (IGF-IR), platelet-derived 
      growth factor receptor and mitogen-activated protein kinase (MAPK) pathway. 
      Current clinical trials are testing the combinations of rapamycin with other 
      kinase inhibitors including IGF-IR, phosphoinositide 3-kinase and 
      MAPK-extracellular signal-regulated kinase inhibitors. SUMMARY: Recent findings 
      on the resistance to rapalogs have stimulated the assessment of combinations of 
      inhibitors in clinical trials. This review summarizes the current knowledge of 
      primary and secondary rapalog resistance, and the current efforts to overcome 
      this resistance.
FAU - Vicier, Cecile
AU  - Vicier C
AD  - aInstitut National de la Sante et de la Recherche Medicale (INSERM) U981 
      bDepartment of Medical Oncology, Gustave Roussy Institute (IGR), Villejuif, 
      France.
FAU - Dieci, Maria V
AU  - Dieci MV
FAU - Andre, Fabrice
AU  - Andre F
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Opin Oncol
JT  - Current opinion in oncology
JID - 9007265
RN  - 0 (Androstadienes)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - NY22HMQ4BX (exemestane)
RN  - P188ANX8CK (Trastuzumab)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Androstadienes/administration & dosage
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Biomarkers, Tumor/metabolism
MH  - Breast Neoplasms/*drug therapy/mortality/pathology
MH  - Clinical Trials as Topic
MH  - Drug Therapy, Combination
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/*drug effects
MH  - Molecular Targeted Therapy/*methods
MH  - Protein Kinase Inhibitors/*administration & dosage
MH  - Receptor, IGF Type 1/*drug effects
MH  - Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage/analogs & derivatives
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Trastuzumab
MH  - Treatment Outcome
EDAT- 2013/10/08 06:00
MHDA- 2014/06/17 06:00
CRDT- 2013/10/08 06:00
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2014/06/17 06:00 [medline]
AID - 10.1097/CCO.0000000000000014 [doi]
PST - ppublish
SO  - Curr Opin Oncol. 2013 Nov;25(6):587-93. doi: 10.1097/CCO.0000000000000014.