HCC Innervation Assessment

Primary liver cancer casualties are ranked 3rd worldwide and are still on the rise despite the recent advent of adequate hepatitis B and C therapies. Genetic diseases of the liver and hepatic comorbidities, such as alcoholic liver disease and metabolic syndrome with metabolic-associated steatohepatitis, are long-term cooperators or independent factors fostering the onset of hepatocellular carcinoma (HCC) and enhancing disease heterogeneity. Though HCC is known to develop in 90% of cases of cirrhosis, its onset and clinical outcomes, in terms of phenotypes and speed of progression, are highly variable from one patient to another. Despite the identification of several potential therapeutic targets, most drugs have failed to exceed the efficacy of currently available compounds. Treatments with tyrosine kinase inhibitors for instance lead to short-term, unavoidable relapse, whereas treatment with immune checkpoints inhibitors or growth factors inhibitors currently provide some hope for only a minority of patients with unresectable HCC. In this respect, cellular/tissular structures linking the general pathophysiology of the patient with HCC may be of interest, as they are patient-specific and may uncover novel ways of defining stratification criteria. In line with such notions, several recent original papers and related commentaries highlighted the relevance of studying cancer neurosciences of peripheral organs. In that context, pathological innervation and autonomous nervous system involvement or dysregulation have been identified in ovarian, prostate, gastric and pancreatic cancers, nurturing tumor stroma and conferring stronger carcinogenic properties. Moreover, the autonomic nervous system post-synaptic receptors have been shown to be favorably actionable in some experimental conditions in cancer. The autonomic nervous system comprises the sympathetic (adrenergic signaling) and parasympathetic (cholinergic signaling) arms that relay signals both ways along the brai