A hormetic response model for glutamine stress in cancer.

Glutamine metabolism supports the development and progression of many cancers and is considered a therapeutic target. Attempts to inhibit glutamine metabolism have resulted in limited success and have not translated into clinical benefit. The outcomes of these clinical studies, along with preclinical investigations, suggest that cellular stress responses to glutamine deprivation or targeting may be modeled as a biphasic hormetic response.

Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.

In pancreatic ductal adenocarcinoma (PDAC), glutamine is a critical nutrient that drives a wide array of metabolic and biosynthetic processes that support tumor growth. Here, we elucidate how 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist that broadly inhibits glutamine metabolism, blocks PDAC tumor growth and metastasis. We find that DON significantly reduces asparagine production by inhibiting asparagine synthetase (ASNS), and that the effects of DON are rescued by asparagine.

VAX014, an Oncolytic Therapy, Reduces Adenomas and Modifies Colon Microenvironment in Mouse Model of CRC.

Colorectal cancer (CRC) remains the third most common form of cancer and, despite its reduced mortality, results in over 50,000 deaths annually, highlighting the need for novel therapeutic approaches. VAX014 is a novel clinical-stage, oncolytic bacterial minicell-based therapy shown to elicit protective antitumor immune responses in cancer, but it has not been fully evaluated in CRC. Here, VAX014 was demonstrated to induce oncolysis in CRC cell lines in vitro and was evaluated in vivo, both as a prophylactic (before spontaneous development of adenomatous polyps) and as a neoadjuvant treatment using the Fabp-CreXApc preclinical animal model of colon cancer.

PIP kinases: A versatile family that demands further therapeutic attention.

Phosphoinositides are membrane-localized phospholipids that regulate a plethora of essential cellular processes. These lipid signaling molecules are critical for cell homeostasis and therefore their levels are strictly regulated by the coordinated action of several families of lipid kinases and phosphatases. In this review, we provide a focused perspective on the phosphatidylinositol phosphate kinase (PIPK) family and the three subfamilies that compose it: Type I PIPKs or phosphatidylinositol-4-phosphate 5-kinases (PI4P5Ks), Type II PIPKs or phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks), and Type III PIPKs or phosphatidylinositol-3-phosphate 5-kinases (PIKfyve).

The Viral Janus: Viruses as Aetiological Agents and Treatment Options in Colorectal Cancer.

In recent years, our understanding of the importance of microorganisms on and within our bodies has been revolutionized by the ability to characterize entire microbial communities. No more so is this true than in cases of disease. Community studies have revealed strong associations between microbial populations and disease states where such concomitance was previously absent from aetiology: including in cancers.