0000000001056404
AUTHOR
N. Funel
Role of hypoxia in pemetrexed-resistance of mesothelioma mediated by proton-coupled folate transporter, and preclinical activity of new anti-LDH compounds
Introduction There are few effective therapies for malignant pleural mesothelioma (MPM), which remains one of the most lethal cancers. We previously demonstrated that low expression of the PCFT transporter, both at mRNA and protein levels, is associated with shorter survival of MPM patients treated with pemetrexed (Giovannetti et al., 2017). Since hypoxia has also been associated to antifolate-resistance (Raz et al, 2014), this study was aimed at elucidating key factors in pemetrexed resistance and hypoxia that may contribute to the rational development of novel therapeutic interventions against mesothelioma. Methods The levels of PCFT and of the hypoxia marker carbonic anhydrase-IX were de…
Impact of phospho-Akt expression on the clinical outcome and activity of gemcitabine and Akt inhibitors in pancreatic ductal adenocarcinoma
Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid tumors. Despite extensive preclinical and clinical research, the prognosis of this disease has not significantly improved, with a 5-year survival rate around 7%. There is an urgent need to better understand the molecular pathology of PDAC in order to improve patient selection for current treatment options and to develop novel therapeutic strategies. The PI3K/AKT/mTOR pathway plays a crucial role in PDAC: activation of Akt is a frequent event and has been correlated to poor prognosis and resistance to chemotherapy. Against this background, effective blockage of Akt signaling can lead to programmed cell death a…