Modern therapeutic approaches for hepatic tumors: progress, limitations, and future directions

Abstract

Hepatic tumors, such as hepatocellular carcinoma (HCC) and metastatic liver malignancies, represent a substantial worldwide health concern due to elevated mortality rates and unfavorable prognoses. Notwithstanding progress in surgical, locoregional, and systemic therapy, significant obstacles like as late-stage diagnosis, treatment resistance, and discrepancies in healthcare access still hinder patient outcomes. This study thoroughly analyzes recent breakthroughs in hepatic tumor treatment, including surgical improvements, immunotherapy, targeted medicines, and nanotechnology-based drug delivery systems. The discourse emphasizes minimally invasive methods including laparoscopic and robotic-assisted hepatectomies, the function of immune checkpoint inhibitors, and the promise of nanoparticle-based therapeutics to improve drug administration while reducing systemic toxicity. This study aims to critically assess current hepatic tumor treatments, examining their effectiveness, constraints, and prospective developments. Critical concerns, such as drug resistance, post-treatment recurrence, and the accessibility of innovative medicines in resource-constrained environments, are addressed. The review underscores the significance of personalized medicine, biomarker-guided treatment approaches, and interdisciplinary teamwork in enhancing therapeutic results. Future research seeks to enhance patient survival and quality of life through the integration of developing technology and the refinement of present treatment approaches.

Keywords: Hepatic tumors; Hepatocellular carcinoma (HCC); Immunotherapy; Liver cancer treatment; Nanotechnology; Surgical innovations.

Fig. 1

Procedural technique encompassing the four phases of SMWA. A The planning phase involves using the navigation system's planning module to choose the skin entry point and the intrahepatic target location. This is done to plan the ideal ablation probe trajectory. The manufacturer's predicted simulated ablation zone is green, the intended ablation margin is orange, and the target tumor is red. B During the navigation phase, the cross-hair viewer is used to indicate the direction of the projected trajectory, and the aiming device is guided along that trajectory. Millimeters denote the trajectory depth for successive ablation probe positions. C Following ablation probe insertion, the positional accuracy of the probe is measured in millimeters and confirmed in the validation scan in relation to the anticipated trajectory. If the results are good, the procedure is called microwave ablation. D The validation of the ablation zone: Direct overlay of pre- and post-ablation pictures with the validation module allows for fast calculation of the completeness of ablation, ensuring that a sufficient ablation zone has been validated [95]

Fig. 2

Liver transplant milestones. Abbreviations: DCD—Cardiac death; DAA—Direct-acting antiviral agent [99]

Fig. 3

Hierarchical cancer immunological microenvironment (HCC) schematic. Specific immune response in HCC is mediated by the invasion of different subpopulations of immune cells, regulatory cytokines, and some inhibitory signals. A number of substances are produced by HCC tumor cells that inhibit the tumoricidal capacity of CTL and NK cells, including hypoxia, IDO, VEFG, IL-10, and TGF-β, IL-10, and inhibitory receptors NKG2 A. Furthermore, in order to entice TANs into the tumor stroma, HCC tumor cells release CXC chemokines, particularly CXCL8. B cell PD-1 signaling activation enhances IL-10 production, which in turn suppresses effector T cell anti-tumor immunity. The cytotoxicity of CTL and NK cells is impaired due to an increase in IL-10 secretion and a decrease in IL-6 and IL-12 secretion caused by the interaction between MDSCs and TAMs. Several cytokines, including VEFG, IL-β, and IL-6, which are produced by CAFs and HSCs, and VEFG and GM-CSF, which are produced by HCC tumor cells, promote the aggregation of MDSCs in the tumor stroma. By interacting with PD-L1 on KCs, which in turn interacts with PD-1 on T cells, MDSCs and KCs facilitate immune evasion. Inducing T cell apoptosis can be achieved by binding Galectin-9 on MDSCs to TIM-3 on T cells. By reducing the production of TNF-α and IFN-γ, Tregs can hinder CTL activation. They can also diminish the anti-tumor activity of NK cells by producing IL-2, IL-8, and TGF-β. In order to inhibit the antitumor response of CTL, DCs can mediate the synthesis of IL-10 and the decrease of IL-12. TAN stands for tumor-associated neutrophil; CAF for cancer-associated fibroblast; NK for natural killer cells; TAM for tumor-associated macrophage; MDSC for myeloid-derived suppressor cell; and CTL for cytotoxic T lymphocyte. The acronyms IDO, KC, DC, IL-10, NKG2 A, TGF-β, GM-CSF, and ICI stand for hepatic stellate cell, kupffer cell, dendritic cell, transforming growth factor β, interleukin-10, vascular endothelial growth factor, granulocyte–macrophage colony-stimulating factor, and immune checkpoint inhibitor, respectively [164]