ACYP1 (Acylphosphatase 1)

Conversely, in glioblastoma (GBM), PDE10A acts as a tumor suppressor, and its knockdown promotes tumor progression via activation of the PI3K/AKT pathway. These findings showed the ability of PDE10A to be considered as a promising biomarker and therapeutic target in oncology; however, it is suggested to examine the tissue-specific expression of PDE10A, baseline cyclic nucleotide levels, cross-talk with other pathways, differences in the degree and duration of PDE10A suppression, and the interplay between PDE10A-mediated cyclic nucleotide signaling and compensatory oncogenic pathways for an effective therapy as observed in other PDEs family reviewed in this manuscript.

Furthermore, PDE10A loss and decreased protein expression corresponded with an epithelial-to-mesenchymal transition (EMT) phenotype in both cohorts, consistent with the known PN-MES shift observed in glioblastoma. In summary, PDE10A loss in colon adenocarcinoma is associated with decreased OS and PFS, more frequent lymphatic invasion, higher pathologic nodal stage, metastatic disease, and an EMT phenotype.

Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro...Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboring PDE10A loss have worse outcomes and potentially increased sensitivity to PI3K inhibition.

Taken together, our study elucidates a novel role for PDE10A in cardiotoxicity induced by DOX and cancer growth. Given that PDE10A has been already proven to be a safe drug target, PDE10A inhibition may represent a novel therapeutic strategy in cancer therapy, with effects preventing DOX-induced cardiotoxicity and simultaneously antagonizing cancer growth.