Chloride intracellular channels in oncology as potential novel biomarkers and personalized therapy targets: a systematic review

Background: The chloride intracellular channels (CLICs) family includes six ion channels (CLIC1-CLIC6) expressed on the cellular level and secreted into interstitial fluid and blood. They are involved in the physiological functioning of multiple systems as well as the pathogenetic processes of cancer. CLICs play essential roles in the tumor microenvironment. The current systematic review aimed at identifying and summarizing the research of CLICs in oncology on clinical material to assess CLICs' potential as novel biomarkers and personalized therapy targets.

Materials and methods: The authors systematically searched the PubMed database for original articles concerning CLIC research on clinical material of all types of cancer - fluids and tissues.

Results: Fifty-three articles investigating in summary 3944 clinical samples were qualified for the current review. Studied material included 3438 tumor samples (87%), 437 blood samples (11%), and 69 interstitial fluid samples (2%). Studies investigated 21 cancer types, mostly hepatocellular carcinoma, colorectal, ovarian, and gastric cancer. Importantly, CLIC1, CLIC2, CLIC3, CLIC4, and CLIC5 were differently expressed in cancerous tissues and patients' blood compared to healthy controls. Moreover, CLICs were found to be involved in several cancer-associated signaling pathways, such as PI3K/AKT, MAPK/ERK, and MAPK/p38.

Conclusion: CLIC family members may be candidates for potential novel cancer biomarkers due to the contrast in their expression between cancerous and healthy tissues and secretion to the interstitial fluid and blood. CLICs are investigated as potential therapeutic targets because of their involvement in cancer pathogenesis and tumor microenvironment.