M echanisms of R esistance to A tezolizumab C ombined with B evacizumab ( a +T) T herapy in A dvanced H epatocellular C arcinoma

Hepatocellular carcinoma has a high degree of malignancy, most of which have been diagnosed in the middle and late stages, and systematic treatment is the main treatment. Atezolizumab combined with bevacizumab is a first-line standard regimen, but primary and secondary drug resistance occurs frequently, which seriously affects the long-term efficacy. The existing research focuses on a single pathway or cell subsets, lacks systematic integration, and the core factors of primary drug resistance and clinical classification system are still unclear. This article starts with the classification of drug resistance, and compares the characteristics of primary and secondary drug resistance; the mechanisms of myeloid cell remodeling, adaptive immunity, immune rejection and tumor dedifferentiation in the microenvironment are described. The three signal axes drive drug resistance through metabolic reprogramming, oxidative stress and macrophage polarization. Drug resistance is a dynamic process of molecular abnormalities and immunosuppression. This paper points out the current deficiencies in mechanism integration, primary initiation and clinical classification, and proposes that in the future, multi-omics and spatial transcriptome technology should be used to construct a multi-dimensional classification system, explore intervention targets, and provide a theoretical reference for individualized reversal strategies.