NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 76(2), P. 446 - 457

Published: Sept. 20, 2021

Language: Английский

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Mechanisms of drug resistance in HCC

Hepatology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 3, 2023

HCC comprises ∼80% of primary liver cancer. is the only major cancer for which death rates have not improved over last 10 years. Most patients are diagnosed with advanced disease when surgical and locoregional treatments feasible or effective. Sorafenib, a multikinase inhibitor targeting cell growth angiogenesis, was approved unresectable in 2007. Since then, other inhibitors been approved. Lenvatinib found to be noninferior sorafenib as first-line agent. Regorafenib, cabozantinib, ramucirumab were shown prolong survival second-line agents. Advances immunotherapy also added hope patients, but their efficacy remains limited. A large proportion gain no long-term benefit from systemic therapy due acquired drug resistance, which, combined its rising incidence, keeps highly fatal disease. This review summarizes mechanisms resistance includes methods bypassing resistance. It addresses recent advancements immunotherapy, provides new perspectives on linkage between molecular etiology HCC, evaluates role microbiome discusses alterations signaling pathways, dysregulation apoptosis, modulations tumor microenvironment, involvement stem cells, changes metabolism/transport, hypoxia, DNA repair, microRNAs Understanding interplay among these factors will provide guidance development therapeutic strategies capable improving patient outcomes.

Language: Английский

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Drug Resistance and Endoplasmic Reticulum Stress in Hepatocellular Carcinoma

Cells, Journal Year: 2022, Volume and Issue: 11(4), P. 632 - 632

Published: Feb. 11, 2022

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide. It usually diagnosed in an advanced stage characterized by a high intrinsic drug resistance, leading to limited chemotherapeutic efficacy relapse after treatment. There therefore vast need for understanding underlying mechanisms that contribute resistance developing therapeutic strategies would overcome this. The rapid proliferation tumor cells, combination with highly inflammatory microenvironment, causes chronic increase protein synthesis different hepatic cell populations. This leads intensified demand folding, which inevitably accumulation misfolded or unfolded proteins lumen endoplasmic reticulum (ER). process called ER stress triggers response (UPR) order restore or—in case severe prolonged stress—to induce death. Interestingly, three arms signaling pathways have been shown drive chemoresistance several tumors could form promising target. review provides overview how activation UPR contributes HCC.

Language: Английский

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Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 2, 2023

While specific cell signaling pathway inhibitors have yielded great success in oncology, directly triggering cancer death is one of the drug discovery challenges facing biomedical research era precision oncology. Attempts to eradicate cells expressing unique target proteins, such as antibody-drug conjugates (ADCs), T-cell engaging therapies, and radiopharmaceuticals been successful clinic, but they are limited by number targets given inability intracellular proteins. More recently, heterobifunctional small molecules Proteolysis Targeting Chimera (PROTACs) paved way for protein proximity inducing therapeutic modalities. Here, we describe a proof-of-concept study using novel called

Language: Английский

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Schisandrin B induces HepG2 cells pyroptosis by activating NK cells mediated anti-tumor immunity

Toxicology and Applied Pharmacology, Journal Year: 2023, Volume and Issue: 472, P. 116574 - 116574

Published: June 2, 2023

Language: Английский

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Construction of a radiogenomic signature based on endoplasmic reticulum stress for predicting prognosis and systemic combination therapy response in hepatocellular carcinoma

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 23, 2025

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Various factors in tumor environment (TME) can lead to activation endoplasmic reticulum stress (ERS), thereby affecting occurrence and development tumors. The objective our study was develop validate a radiogenomic signature based on ERS predict prognosis systemic combination therapy response. Using data from Cancer Genome Atlas Program (TCGA) as training cohort International cancer genome consortium (ICGC) testing cohort. Univariate Cox regression multivariate analysis were used identify prognostic-related genes construct model. HCC single-cell obtained Gene Expression Omnibus (GEO) map gene signatures explore inter-cellular signaling communications. Finally, response rate (ORR) overall survival (OS). A total four related ERS, including Stanniocalcin-2 (STC2), Melanoma-Associated Antigen 3 (MAGEA3), BR Serine/Threonine-Protein Kinase 2 (BRSK2), DEAD/H-Box Helicase 11 (DDX11) identified. Macrophages significantly different between high-risk low-risk groups. group showed higher targeting programmed cell death-1 (PD-1) mutated protein p53 (TP53) scores. Drug sensitivity found that sensitive drugs target phosphatidylinositol 3-kinase/ mechanistic rapamycin (PI3K/mTOR) pathway. Further research revealed expression STC2 endothelial cells (ECs), particularly plasmalemma vesicle associated (PLVAP) + ECs, may regulate reprogramming function macrophages. Furthermore, we identified nine radiomic features established therapy. This guide for patients with unresectable HCC. We an prognostic model patient prognosis. also closely TME mainly manifested interaction tumor-associated (TAEs) macrophages (TAMs). Moreover, constructed ERS. subsequent

Language: Английский

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In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(1), P. e001481 - e001481

Published: Jan. 1, 2021

Background Uveal melanoma (UM) is the most frequent intraocular malignancy and resistant to immunotherapy. Nearly 50% of patients with UM develop metastatic disease, overall survival outcome remains very poor. Therefore, a treatment regimen that simultaneously targets primary prevents metastasis needed. Here, we suggest an immunotherapeutic strategy for involving combination local photodynamic therapy (PDT), rho-kinase (ROCK) inhibitor, PD-1/PD-L1 immune checkpoint blockade. Methods The antitumor efficacy response monotreatment or combinational were evaluated in B16F10-bearing syngeneic mouse models. Abscopal responses induced by triple-combinational validated bilateral B16F10 After each treatment, profiles functional examinations assessed tumors tumor draining lymph nodes flow cytometry, ELISA, immunofluorescence assays. In orthotopic models, location infiltrate microenvironment (TME) was after multiplex immunohistochemistry nodules monitored. Results PDT Ce6-embedded nanophotosensitizer (FIC-PDT) elicited immunogenic cell death stimulated antigen-presenting cells. situ clearance FIC-PDT ripasudil, clinically approved ROCK cells, which turn primed tumor-specific cytotoxic T Moreover, sensitized blockade reconstruct TME phenotypes cold into hot tumors, resulting recruitment robust CD8 + cells TME, propagation systemic immunity mediate abscopal effects, prolonged survival. immune-privileged model, even low-dose ripasudil combined anti-PD-L1 antibody reduced burden prevented metastasis. Conclusions A localized inhibitor exerted cancer vaccine-like function. Immunogenic led trafficking site evoke inhibit metastasis, one major challenges therapy. Thus, could be potent UM.

Language: Английский

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Nanotheranostics: A powerful next-generation solution to tackle hepatocellular carcinoma

World Journal of Gastroenterology, Journal Year: 2022, Volume and Issue: 28(2), P. 176 - 187

Published: Jan. 7, 2022

Hepatocellular carcinoma (HCC) is an epidemic burden and remains highly prevalent worldwide. The significant mortality rates of HCC are largely due to the tendency late diagnosis multifaceted, complex nature treatment. Meanwhile, current therapeutic modalities such as liver resection transplantation only effective for resolving early-stage HCC. Hence, alternative approaches required improve detection enhance efficacy treatment options. Nanotheranostic platforms, which utilize biocompatible nanoparticles perform both diagnostics targeted delivery, has been considered a potential approach cancer management in past few decades. Advancement nanomaterials biomedical engineering techniques led rapid expansion nanotheranostics field, allowing more sensitive specific diagnosis, real-time monitoring drug enhanced efficacies across various malignancies. focus this review on applications first explores epidemiology commonly encountered obstacles It then presents technological functional advancements nanotheranostic technology general, specifically use promising option address key challenges present management.

Language: Английский

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Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers

Cancers, Journal Year: 2022, Volume and Issue: 14(14), P. 3524 - 3524

Published: July 20, 2022

Hepatobiliary, pancreatic, and gastrointestinal cancers account for 36% of the ten million deaths caused by cancer worldwide every year. The two main reasons this high mortality are their late diagnosis refractoriness to pharmacological treatments, regardless whether these based on classical chemotherapeutic agents, targeted drugs, or newer immunomodulators. Mechanisms chemoresistance (MOC) defining multidrug resistance (MDR) phenotype each tumor depend synergic function proteins encoded more than one hundred genes classified into seven groups (MOC1-7). Among them, efflux active agents from cells across plasma membrane members superfamily ATP-binding cassette (ABC) (MOC-1b) plays a crucial role in determining MDR. Although families human ABC known, only few pumps (mainly MDR1, MRP1-6, BCRP) have been associated with reducing drug content hence inducing hepatobiliary, cells. present descriptive review, which compiles updated information expression proteins, will be helpful because there is still some confusion actual relevance response regimens currently used treating cancers. Moreover, we aim define MOC pattern tumor-by-tumor basis, even dynamic way, it can vary during progression chemotherapy. This indispensable developing novel strategies sensitization.

Language: Английский

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Autophagy orchestrates resistance in hepatocellular carcinoma cells

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114487 - 114487

Published: March 22, 2023

Treatment resistance is one of the major barriers for therapeutic strategies in hepatocellular carcinoma (HCC). Many studies have indicated that chemotherapy and radiotherapy induce autophagy machinery (cell protective autophagy) HCC cells. In addition, many experiments report a remarkable crosstalk between treatment pathways. Thus, could be key factors enabling tumor cells to hinder induced cell death after medical interventions. Therefore, extensive research on molecular pathways involved induction been conducted achieve desired response. The related therapy are TGF-β, MAPK, NRF2, NF-κB, non-coding RNAs. EMT, drug transports, apoptosis evasion, DNA repair, cancer stem cells, hypoxia considerable impact hepatoma cell's response therapies. These mechanisms protect against various treatments shown each them connected HCC. Hence, inhibition may an effective strategy improve outcome patients. this review, we further highlight how leads poor during through complex network it enhances primary liver cancer. We propose combinational regimens approved protocols plus inhibitors overcome therapy.

Language: Английский

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