Gastric cancer (GC) is a predominant malignant neoplasia responsible for cancer death worldwide. Because of the difficulty in early diagnosis as well as its high metastasis rate, GC shows an increasing incidence and poor prognosis. Conventional treatments for GC, such as chemotherapy, radiotherapy, and surgical resection, still fail to achieve curative effects because of drug resistance, a mechanism that leads to a reduction of 5-year survival for GC patients. Anoikis, a particular type of programmed cell death, is activated upon cancer cell detachment from the extracellular matrix, playing a crucial role in antagonizing the progression of several malignant tumors. Because GC cells metastasize mainly in the nearby sites in the peritoneum, a better comprehension of the molecular mechanisms involved in the anchorage-independent growth as well as metastatic spreading is crucial to counteract GC progression. In this context, this review critically examines the molecular mechanisms of anoikis, key pathways and regulatory networks, and the role of anoikis resistance in GC. Furthermore, it summarizes potential therapeutic strategies for targeting anoikis-resistant cells. By collecting and analyzing existing literature, this work aims to bridge gaps in the comprehension of the relation between anoikis resistance and GC pathophysiology, providing novel insights and directions for future research in this field.

Gastric cancer (GC) is a neoplasia with an increase in incidence and mortality over the next years. Currently, the treatment of this malignancy consists of surgery in association with the administration of platinum compounds or 5-FU capecitabine. The identification of novel biomarkers related to the GC progression is a key point in re-modulating the pharmacological treatment to get a more efficient patient response. In this study, we reported that Hormonally Upregulated Neu tumor-associated Kinase (HUNK) promotes gastric cancer progression by regulating cell homeostasis. Particularly, we demonstrated that HUNK is responsible for the increase in gastric cancer cell proliferation through the binding and phosphorylation of p38 MAP kinase and that its depletion is associated with a reduction of survival both in gastric cancer cells and patient-derived organoids. Further, we reported that HUNK regulates positively the expression of MUC16/CA-125, a well-known cancer prognostic marker. Our findings shed light, for the first time, on the molecular mechanisms regulated by HUNK in gastric cancer cells making this kinase a promising candidate for novel targeted therapeutic strategies.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition, with therapy-resistant patients undergoing surgery and a high risk of developing colorectal cancer. Novel therapeutic approaches have shown limited efficacy in IBD treatment, highlighting the need for safer and more personalized strategies. The potential of natural compounds to modulate inflammation suggests their use as a potential adjunct therapy for IBD patients. Methods: Intestinal epithelial cells organoids (IECOs) were derived from IBD and non-IBD tissues from IBD patients, and levels of inflammation markers and epithelial barrier permeability were assayed using qRT-PCR, WB, IF and leaking assays in the presence of Ozoile, an extra virgin olive oil enriched in ozonides. The Luciferase-based IBD-like organoid platform was generated for preliminary screening of anti-inflammatory drugs. Results: In this study, we showed that IBD-ECOs recapitulate tissue architecture and pathological state. We showed that Ozoile has anti-inflammatory and epithelial barrier modulatory effects and that the Luciferase IBD-like organoid model is sensitive to anti-inflammatory compounds. Conclusions: Using IECOs, the specific anti-inflammatory and regenerative properties of Ozoile were assessed. Notably, our study highlights the potential of an IBD-like organoid platform to use in high-throughput screenings for rapid selection of anti-inflammatory drugs.