Hepatocellular Cancer

P=N/A, N=19019, Completed, Tongji University

With respect to drug response, PRKD1-high HCC cases exhibited increased predicted sensitivity to multiple tyrosine kinase inhibitors (TKIs), while in vitro PRKD1 knockdown reduced sorafenib sensitivity, and sorafenib treatment suppressed both PRKD1 and p-ERK1/2 levels. Collectively, our findings identify PRKD1 as a multifaceted contributor to HCC progression, immune microenvironment modulation, and TKI responsiveness. These results highlight PRKD1 as a promising therapeutic target warranting further mechanistic and translational investigation.

Thus, prolonged ATF6α activation drives ER stress, leading to glycolysis-dependent immunosuppression in liver cancer and sensitizing to ICB. Our findings suggest that persistently activated ATF6α is a tumour driver, a potential stratification marker for ICB response and a therapeutic target for HCC.

These studies highlighted that GA may inhibit oxidative stress to ameliorate hepatocellular carcinoma via the Nrf2-pSmad2C/2L pathway. However, the specific interaction regulatory mechanism deserves further exploration.

Our findings demonstrate that ELOVL3 correlates with cancer cell stemness and angiogenic potential, thereby identifying it as a promising therapeutic target. Further investigations are warranted to elucidate the downstream molecular pathways that mediate these functional effects.

Herein, guided by the structural features of Sorafenib, the selective Bcl-2 inhibitor Venetoclax, and the selective Mcl-1 inhibitor AZD5991, we designed and synthesized a series of novel Sophocarpine-derived analogues bearing a pyridylethyl moiety via a molecular-hybridization strategy. In parallel, a 3D-QSAR (CoMFA) model was constructed to rationalize the structure-activity relationship and to inform further lead optimization. Collectively, these findings identify S6 as a promising Sophocarpine derivative with a putative dual Bcl-2/Mcl-1 targeting profile, with significant anti-HCC activity and potential for preclinical development.

Moreover, 4 exhibited a high selectivity index toward Hep-G2 cells (SI = 260.00) and inhibited the migration and invasion of Hep-G2 cells. These findings may serve as a valuable reference for the development of novel FASN inhibitors exhibiting potent anti-hepatocellular carcinoma activity.

USP21 stabilizes SMARCB1 under hypoxic conditions, thereby sustaining its oncogenic and immunosuppressive activities in HCC. Targeting the USP21-SMARCB1 axis may inhibit tumor growth and enhance immunotherapy responsiveness, offering a potential therapeutic strategy for overcoming resistance in HCC treatment.

P3, N=959, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

GBHP01 may contribute to shifts in gut microbial composition by elevating probiotic species (L. reuteri and L. murinus) and reducing inflammatory taxa (Bilophila and Mucispirillum), suggesting its potential as a dietary intervention against HFD-induced metabolic disorders.

Patients with the PNPLA3 CG/GG genotype, especially those with progressive fibrosis, have a high risk of recurrence after liver resection. PNPLA3 genotyping may help identify patients at high risk of late recurrence who require careful long-term surveillance.