Combination Treatment of Resistant Acute Promyelocytic Leukemia Cells with Arsenic Trioxide and Anti-Apoptotic Gene Inhibitors.

Background: Arsenic trioxide (ATO) is an anticancer agent for treating acute promyelocytic leukemia (APL). However, 5-10% of patients fail to respond, developing relapsed/refractory disease. The aim of this study was to identify potential new therapeutic approaches for ATO-unresponsive APL by targeting the anti-apoptotic genes that contribute to drug resistance.

Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies.

Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy.

Using to Dissect the Roles of the mTOR Signaling Pathway in Cell Growth.

The evolutionarily conserved target of rapamycin (TOR) serine/threonine kinase controls eukaryotic cell growth, metabolism and survival by integrating signals from the nutritional status and growth factors. TOR is the catalytic subunit of two distinct functional multiprotein complexes termed mTORC1 (mechanistic target of rapamycin complex 1) and mTORC2, which phosphorylate a different set of substrates and display different physiological functions. Dysregulation of TOR signaling has been involved in the development and progression of several disease states including cancer and diabetes.

GOLPH3 protein controls organ growth by interacting with TOR signaling proteins in Drosophila.

The oncoprotein GOLPH3 (Golgi phosphoprotein 3) is an evolutionarily conserved phosphatidylinositol 4-phosphate effector, mainly localized to the Golgi apparatus, where it supports organelle architecture and vesicular trafficking. Overexpression of human GOLPH3 correlates with poor prognosis in several cancer types and is associated with enhanced signaling downstream of mTOR (mechanistic target of rapamycin). However, the molecular link between GOLPH3 and mTOR remains elusive.