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Current Strategies to Identify Patients That Will Benefit from TACE Treatment and Future Directions a Practical Step-by-Step Guide.

ABSTRACT: Treatment of hepatocellular carcinoma (HCC) depends on the stage of disease. In the Western Hemisphere, the Barcelona Clinic Liver Cancer classification (BCLC) is the preferred staging system. Approximately one-third of patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. However, the intermediate-stage comprises a heterogeneous subgroup of patients with considerable differences in tumor burden and liver function. In addition, differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Due to these differences, not all patients benefit equally from TACE. Several tools and scoring systems have been devised to provide decision-making support. All of these have shown promising initial results but failed external evaluation and have not been translated to the clinic. Nevertheless, criteria for objectifying treatment decisions in daily clinical practice are needed in all stages of disease. Therefore, this review provides a concise practical step-by-step guide on current strategies for patient selection and decision-making, with a focus on TACE, to critically evaluate the existing decision-support tools and provide a summary of the latest updates in the field.

SUBMITTER: Muller L

PROVIDER: S-EPMC8128497 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Glucocorticoids are the most effective anti-inflammatory therapy for asthma yet are relatively ineffective in chronic obstructive pulmonary disease. Glucocorticoids suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, by reversing histone acetylation of activated inflammatory genes through binding of ligand-bound glucocorticoid receptors (GR) to co-activator molecules and recruitment of histone deacetylase-2 to the activated inflammatory gene transcription complex (trans-repression). At higher concentrations of glucocorticoids GR homodimers interact with DNA recognition sites to activate transcription through increased histone acetylation of anti-inflammatory genes and transcription of several genes linked to glucocorticoid side effects (trans-activation). Glucocorticoids also have post-transcriptional effects and decrease stability of some pro-inflammatory mRNA species. Decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have now been identified which involve post-translational modifications of GR. Histone deacetylase-2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of glucocorticoids. Dissociated glucocorticoids and selective GR modulators which show improved trans-repression over trans-activation effects have been developed to reduce side effects, but so far it has been difficult to dissociate anti-inflammatory effects from adverse effects. In patients with glucocorticoid resistance alternative anti-inflammatory treatments are being investigated as well as drugs that may reverse the molecular mechanisms of glucocorticoid resistance.

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Current Strategies to Identify Patients That Will Benefit from TACE Treatment and Future Directions a Practical Step-by-Step Guide.

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