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…