PMID- 22960556
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20211203
IS  - 1531-703X (Electronic)
IS  - 1040-8746 (Linking)
VI  - 24
IP  - 6
DP  - 2012 Nov
TI  - Phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway 
      inhibition: a breakthrough in the management of luminal (ER+/HER2-) breast 
      cancers?
PG  - 623-34
LID - 10.1097/CCO.0b013e328358a2b5 [doi]
AB  - PURPOSE OF REVIEW: Recent data from clinical trials evaluating mammalian target 
      of rapamycin (mTOR) inhibitors in the setting of endocrine resistance in luminal 
      (estrogen receptor-positive, human epidermal growth factor receptor 2-negative) 
      breast cancers have validated this pathway as a bona-fide therapeutic target in 
      this setting. There are currently many agents under clinical investigation that 
      inhibit the phosphatidylinositol 3-kinase (PI3K) pathway. We review these 
      findings in the context of the preclinical data and the current status of 
      biomarker development in this field. RECENT FINDINGS: Clinical trials in the 
      neoadjuvant (RAD2222) and metastatic setting (TAMRAD, BOLERO-2) have reported 
      improved clinical outcome of patients with unselected luminal breast cancer 
      through the addition of mTOR inhibitors to standard endocrine treatment. PI3K 
      molecular aberrations are frequently found in luminal breast cancer, yet the role 
      of these in defining patients' prognosis and response to PI3K/AKT/mTOR inhibitors 
      remains to be determined. SUMMARY: Therapeutic targeting of the PI3K pathway 
      promises improved clinical outcome for patients with luminal breast cancer. 
      Correspondingly, agents that target this pathway are entering the clinic at an 
      unprecedented rate. Future clinical trials that incorporate correlative 
      translational research will help us decipher important information critical for 
      successful development of these agents in breast cancer: which part of the 
      pathway should be targeted and in which clinical scenario; and which patients are 
      more likely to benefit from these drugs, particularly in the adjuvant setting.
FAU - Zardavas, Dimitrios
AU  - Zardavas D
AD  - BrEAST Data Center, Institut Jules Bordet, Brussels, Belgium.
FAU - Fumagalli, Debora
AU  - Fumagalli D
FAU - Loi, Sherene
AU  - Loi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Curr Opin Oncol
JT  - Current opinion in oncology
JID - 9007265
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Breast Neoplasms/*drug therapy/genetics/metabolism
MH  - Clinical Trials as Topic
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/pharmacology/therapeutic use
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
EDAT- 2012/09/11 06:00
MHDA- 2013/03/30 06:00
CRDT- 2012/09/11 06:00
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
AID - 10.1097/CCO.0b013e328358a2b5 [doi]
PST - ppublish
SO  - Curr Opin Oncol. 2012 Nov;24(6):623-34. doi: 10.1097/CCO.0b013e328358a2b5.