@entity3620 is a highly chemoresistant solid @entity5 . We have studied this apoptotic resistance using in vitro and ex vivo three-dimensional models, which acquire a high level of chemoresistance that can be reduced by PI3K/ @entity3470 inhibitors. Here, we investigate the activity of @entity28911 , a novel dual PI3K/ @entity3470 inhibitor, which has been proposed to be effective in @entity2615 . In this work, we aimed to identify mechanisms and markers of efficacy for @entity28911 by utilizing 3D models of @entity2615 , both in vitro multicellular spheroids and ex vivo @entity5 fragment spheroids grown from @entity1 @entity5 samples. We found that a subset of @entity2615 spheroids is sensitive to @entity28911 alone and to its combination with chemotherapy. Unexpectedly, this sensitivity did not correlate with the activation of the Akt/ @entity3470 pathway. Instead, sensitivity to @entity28911 correlated with the presence of constitutive @entity16863 puncta, a feature of autophagy, a cellular program that supports cells under stress. In @entity5 fragment spheroids grown from 21 @entity5 , we also found a subset (n = 11) that was sensitive to @entity28911 , a sensitivity that also correlated with the presence of @entity16863 puncta. Interference with autophagy by siRNA of @entity10615 , an essential autophagic protein, increased the response to chemotherapy, but only in the sensitive multicellular spheroids. In the spheroids resistant to @entity28911 , autophagy appeared to play no role. In summary, we show that @entity28911 is effective in @entity2615 3D models that display @entity16863 puncta, and that blockade of autophagy increases their response to chemotherapy. For the first time, we show a role for autophagy in the response to chemotherapy of 3D models of @entity2615 and propose @entity16863 as a potential biomarker of the therapeutic responsiveness of @entity2615 .

Autophagy Correlates with the Therapeutic Responsiveness of XXXX in 3D Models.

@entity1 :: ('9606', 'Species') :: ['patient'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity16863 :: ('9776', 'Gene') :: ['ATG13'] @entity2615 :: ('MESH:D008654', 'Disease') :: ['mesothelioma'] @entity28911 :: ('MESH:C569670', 'Chemical') :: ['GDC-0980'] @entity3620 :: ('MESH:C562839', 'Disease') :: ['Malignant pleural mesothelioma'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity10615 :: ('10533', 'Gene') :: ['ATG7']
@entity3620 :: (MESH:C562839,Disease) :: ['Malignant Pleural Mesothelioma']
