PMID- 25645727
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20191210
IS  - 1744-7658 (Electronic)
IS  - 1354-3784 (Linking)
VI  - 24
IP  - 3
DP  - 2015 Mar
TI  - Buparlisib , an oral pan-PI3K inhibitor for the treatment of breast cancer.
PG  - 421-31
LID - 10.1517/13543784.2015.1008132 [doi]
AB  - INTRODUCTION: Deregulation of the phosphatidylinositol-3-kinase 
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) intracellular signaling pathway 
      is common in breast cancer (BC) and has been found to be potentially implicated 
      in resistance to endocrine and anti-HER2 therapies. Targeting the PI3K/Akt/mTOR 
      pathway may remove this inhibition and restore sensitivity to these compounds. 
      Buparlisib (BKM120) is a potent oral pan-class I PI3K inhibitor that is being 
      extensively evaluated in multiple tumor types. AREAS COVERED: This review briefly 
      summarizes the pharmacodynamics and pharmacokinetics of buparlisib, focusing on 
      preclinical and clinical data in BC and on ongoing randomized trials. EXPERT 
      OPINION: Overall, buparlisib is a safe and tolerable drug and, despite its 
      peculiar toxicity profile, it is suitable for studies in combination with other 
      anticancer agents in BC. Early-phase clinical trials in BC have provided evidence 
      of antitumor activity. Several trials are being conducted in all the biological 
      subsets of BC, including combinations with endocrine therapy, anti-HER2 agents, 
      PARP-inhibitors and chemotherapy. While clinical results are eagerly awaited, 
      biological material suitable for both genomic and non-genomic analyses is being 
      collected. The authors expect an intense investigation of the potential 
      biomarkers that explain response or resistance to buparlisib and inspire 
      strategies to rationally explore the therapeutic potential of this drug.
FAU - Geuna, Elena
AU  - Geuna E
AD  - Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia 
      (FPO) - Candiolo Cancer Center (IRCCs), Institute for Cancer Research and 
      Treatment of Candiolo , Strada Provinciale 142, Km 3.95, CAP 10060, Candiolo, 
      Turin , Italy +39 0119933958 ; +39 0119621525 ; andrea.milani@ircc.it.
FAU - Milani, Andrea
AU  - Milani A
FAU - Martinello, Rossella
AU  - Martinello R
FAU - Aversa, Caterina
AU  - Aversa C
FAU - Valabrega, Giorgio
AU  - Valabrega G
FAU - Scaltriti, Maurizio
AU  - Scaltriti M
FAU - Montemurro, Filippo
AU  - Montemurro F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150203
PL  - England
TA  - Expert Opin Investig Drugs
JT  - Expert opinion on investigational drugs
JID - 9434197
RN  - 0 (Aminopyridines)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Morpholines)
RN  - 0 (NVP-BKM120)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
SB  - IM
MH  - Aminopyridines/adverse effects/pharmacology/*therapeutic use
MH  - Animals
MH  - Antineoplastic Agents/adverse effects/pharmacology/therapeutic use
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - Morpholines/adverse effects/pharmacology/*therapeutic use
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - HER2-directed therapy
OT  - breast cancer
OT  - buparlisib
OT  - chemotherapy
OT  - endocrine therapy
OT  - mammalian target of rapamycin
OT  - phosphatidylinositol-3-kinase
EDAT- 2015/02/04 06:00
MHDA- 2015/09/22 06:00
CRDT- 2015/02/04 06:00
PHST- 2015/02/04 06:00 [entrez]
PHST- 2015/02/04 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
AID - 10.1517/13543784.2015.1008132 [doi]
PST - ppublish
SO  - Expert Opin Investig Drugs. 2015 Mar;24(3):421-31. doi: 
      10.1517/13543784.2015.1008132. Epub 2015 Feb 3.