title: Buparlisib , an oral pan-PI3K inhibitor for the treatment of breast cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This review briefly summarizes the pharmacodynamics and pharmacokinetics of buparlisib, focusing on preclinical and clinical data in BC and on ongoing randomized trials.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Elena
authors: E
authors: Geuna
authors: Andrea
authors: A
authors: Milani
authors: Rossella
authors: R
authors: Martinello
authors: Caterina
authors: C
authors: Aversa
authors: Giorgio
authors: G
authors: Valabrega
authors: Maurizio
authors: M
authors: Scaltriti
authors: Filippo
authors: F
authors: Montemurro
mesh_terms: D000631:Aminopyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009025:Morpholines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D009025:Morpholines; C571178:NVP-BKM120; D000081082:Phosphoinositide-3 Kinase Inhibitors
keywords: HER2-directed therapy; breast cancer; buparlisib; chemotherapy; endocrine therapy; mammalian target of rapamycin; phosphatidylinositol-3-kinase