Anoikis resistance in gastric cancer: a comprehensive review

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.