Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma

1. Download high-res image (139KB)
2. Download full-size image

     

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

1. Download high-res image (274KB)
2. Download full-size image

     

Buparlisib,an oral pan-PI3K inhibitor for the treatment of breast cancer

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.