Malignant peripheral nerve sheath tumors are rare, aggressive soft tissue sarcomas lacking meaningful treatment options. Here (doi.org/10.1172/JCI201331), Angela C. Hirbe @AngelaHirbe & team @washumedicine show dual inhibition with FAK and RAF/MEK overcomes resistance, suppresses growth, and induces tumor regression in preclinical studies of chromosome 8 gain malignant peripheral nerve sheath tumors. @sargoshoe @the_asci #MPNST #Sarcoma

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Carlos L. Arteaga & colleagues present: PI3K signaling in #BreastCancer: therapeutic advances versus adaptive resistance: doi.org/10.1172/JCI207635 Mutations in the PI3K pathway are common oncogenic drivers of breast cancer, but therapeutically targeting the pathway has proved challenging. In this review, Fabiana Napolitano @md_napolitano, Carlos L. Arteaga @CarlosArteagaMD et al. @UTSWMedCenter provide an up-to-date synthesis of PI3K inhibitor development and offer insights into how our understanding of resistance mechanisms will guide future efforts for rational therapeutic sequencing. @the_asci

🧵 1/2: We previously posted about Kim et al. as a landmark in cardiac metabolism. ✏️ In a recent Letter to the Editor, Rong Tian @TianLab @UW & E. Douglas Lewandowski @OhioState discuss the challenges of interpreting double deletion data in the absence of similar analysis for each gene deletion: doi.org/10.1172/JCI209270 Making sense of cardiomyopathy caused by deletion of acetyl-CoA carboxylase 1 and 2 #LetterToTheEditor @the_asci

Dietary fats drive aberrant tissue repair in #obesity: doi.org/10.1172/JCI205829 Obesity is linked to impaired healing, including #HeterotopicOssification (HO), or bone formation, at the injury site. Benjamin Levi & team @UTSW_Surgery implicate dietary #Omega6 lipids in this elevated risk for HO. Image: High-fat diet increased COX-2 expression (green) at the HO site in a mouse model. COX-2 dependent prostaglandin E2 production promoted osteochondral differentiation in mesenchymal progenitor cells. @aaronwjames_lab @BTBKGMD @the_asci

Proposing a combination treatment for reducing death from cerebral malaria: doi.org/10.1172/JCI202285 Alvin H. Schmaier @AlvinSchmaier & team @cwru report on a role for bradykinin in cerebral malaria and find plasma kallkrein inhibitors target host-mediated vascular dysfunction. Combination treatment using kallikrein inhibition and artesunate showed therapeutic benefit in mouse models. @the_asci #CerebralMalaria