Inhibition of the PI3K/AKT/mTOR signaling promotes an M1 macrophage switch by repressing the ATF3-CXCL8 axis in Ewing sarcoma.

Ewing sarcomas are aggressive pediatric tumors of bone and soft tissues driven by in frame chromosomal translocations that yield fusion proteins guiding the oncogenic program. Promising alternative strategies to ameliorate current treatments involve inhibition of the PI3K/AKT/mTOR pathway. In this study, we identified the activating transcription factor 3 (ATF3) as an important mediator of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer and current treatments exert small effects on life expectancy. The most common adjuvant treatment for PDAC is gemcitabine. However, relapse almost invariably occurs and most patients develop metastatic, incurable disease.

Alternative polyadenylation of ZEB1 promotes its translation during genotoxic stress in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. The standard chemotherapeutic drug, gemcitabine, does not offer significant improvements for PDAC management due to the rapid acquisition of drug resistance by patients. Recent evidence indicates that epithelial-to-mesenchymal transition (EMT) of PDAC cells is strictly associated to early metastasization and resistance to chemotherapy.

hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.

Ewing sarcomas (ES) are biologically aggressive tumors of bone and soft tissues for which no cure is currently available. Most ES patients do not respond to chemotherapeutic treatments or acquire resistance. Since the PI3K/AKT/mTOR axis is often deregulated in ES, its inhibition offers therapeutic perspective for these aggressive tumors.

Alternative splicing and cell survival: from tissue homeostasis to disease.

Most human genes encode multiple mRNA variants and protein products through alternative splicing of exons and introns during pre-mRNA processing. In this way, alternative splicing amplifies enormously the coding potential of the human genome and represents a powerful evolutionary resource. Nonetheless, the plasticity of its regulation is prone to errors and defective splicing underlies a large number of inherited and sporadic diseases, including cancer.