Hepatocellular carcinoma (HCC) remains a major fatal disease, and recombinant adeno-associated virus-thymidine kinase/ganciclovir (rAAV-tk/GCV) therapy is a newly discovered gene therapy with a unique mechanism of action for HCC...Finally, this article clarifies the main directions for translational research, including conducting follow-up clinical trials with intensive AFP sample collection, combining imaging detection and multi-omics analysis, and constructing of model-based decision-making models. It also proposes that the rational application of AFP kinetics based on its mechanism of action holds promise for significantly improving the optimization and clinical acceptance of rAAV-tk/GCV therapy in HCC.

Here, we found that multiple lipid metabolism processes are aberrantly activated in Ara-C resistant AML cells, accompanied by upregulation of JAK-STAT3 signaling and key lipid metabolic regulators, notably SREBP1 and CPT2...Our findings highlight the critical role of STAT3-driven lipid metabolism reprogramming in chemoresistance. Furthermore, W1307 emerges as a promising therapeutic candidate to overcome chemoresistance in leukemia treatment.

We conclude that KIT mutations, especially exon 17, confer a high-risk phenotype in otherwise favorable pediatric AML1::ETO AML. Our exploratory data suggest this may be associated with a chemoresistant profile, potentially driven by SOCS1-associated JAK-STAT dysregulation. These findings highlight the necessity of refined risk stratification based on KIT exon profiling and support targeting the SOCS1/JAK-STAT axis to overcome therapy resistance.

pFAO blockade synergizes with chemotherapy drugs such as venetoclax and cytarabine, enabling exploitation of metabolic vulnerabilities to improve therapeutic outcomes. Integrating solid tumor and leukemia insights, peroxisomes emerge as dynamic lipid-processing organelles coupling FAO, redox buffering, and inter-organelle exchange to cancer persistence. Targeting peroxisome-mediated lipid delivery offers a frontier for overcoming metabolic resilience and therapeutic resistance in leukemia.

As an exploratory analysis, subtype-specific therapeutic vulnerabilities were revealed: Subtype A displays predicted sensitivity to immune checkpoint inhibitors (anti-PD-1) and tipifarnib, whereas Subtype B responds better to cytarabine/doxorubicin. Crucially, experimental validation confirmed significant upregulation of key model genes (HIP1, SQLE, VNN1) in AML patient samples and cell lines (P < 0.05), reinforcing the model's biological relevance. These findings establish PCD dysregulation as a central axis of AML heterogeneity, providing a framework for precision risk stratification and hypothesis-generating immunophenotype-guided therapy.

ORR was 57%, 20% and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMA) and BSC (including low intensity treatments as hydroxyurea and low-dose cytarabine), respectively. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.

P=N/A, N=100, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna | Not yet recruiting --> Recruiting | Trial completion date: Jun 2022 --> Feb 2028 | Trial primary completion date: May 2022 --> Feb 2027

Furthermore, USP30 enhanced Ara-C resistance in AML cells in vivo. Together, USP30 promoted Ara-C resistance in AML by deubiquitinating and stabilizing FOXM1, thereby enhancing tumor growth and cell survival.

miR-2110 functions as an upregulated but tumor-suppressive miRNA in AML. The miR-2110-ELK1 axis contributes to regulation of AML cell growth, apoptosis-related signaling, and Ara-C responsiveness, providing a potential molecular basis for further investigation of miRNA-mediated therapeutic modulation in AML.

Functional analyses demonstrated that altered ABCB6 expression did not significantly affect cell proliferation or apoptosis; however, targeted knockdown of ABCB6 markedly restored the sensitivity of K562/A02 cells to adriamycin (ADR) and cytosine arabinoside (Ara-C). Mechanistic studies revealed that ABCB6 contributes to ADR efflux from leukemia cells, thereby reducing intracellular drug accumulation and weakening its cytotoxic activity. Together, these findings establish ABCB6 as a previously unrecognized efflux transporter that contributes to MDR in leukemia and highlight ABCB6 as a potential therapeutic target for overcoming MDR.

Concurrently, it suppresses Polo-like kinase 1 (PLK1) expression, thereby inducing G2/M cell cycle arrest and activating apoptotic pathways. Collectively, our findings identify NTZ as a potent anti-tumor agent and chemosensitizer that restores Ara-C responsiveness, offering a promising combinatorial strategy for the treatment of refractory AML.

Traditional IT agents such as methotrexate or cytarabine were generally associated with modest survival outcomes, whereas more recent studies evaluating IT pemetrexed and molecularly guided regimens reported longer survival in selected cohorts, particularly in EGFR-mutant NSCLC-LM. Ommaya reservoir-based delivery may offer practical advantages for repeated treatment and CSF monitoring in appropriately selected patients, with acceptable toxicity and manageable device-related risks. Emerging data on pemetrexed-based intrathecal regimens and other molecularly informed approaches suggest potential benefit in selected subgroups, but prospective, multicenter, mutation-stratified studies are needed to refine patient selection, optimize dosing strategies, and define the comparative role of different intrathecal delivery routes.