Jingzhuda (entinostat)

The clinical use of the anticancer drug doxorubicin (Dox) is limited by irreversible cardiotoxicity...Therefore, we comparatively investigated the response of murine embryonic stem cells (mESC), endothelial progenitor cells (EC d4) and terminally differentiated endothelial-like cells (EC d6) following exposure to Dox and selected pharmacological inhibitors of DNA repair/DNA damage response (DDR) (RAD51i B02; HDACi entinostat (EST))...Notably, drug treatment of EPC (EC d4) causes multiple dysfunctions in differentiated EC d6. Hence, pharmacological measures aiming to specifically protect EPC from Dox-induced damage are suggested to foster the maintenance of healthy endothelial functionality during regeneration, thereby lowering the risk of detrimental late cardiotoxicity resulting from Dox-based anticancer regimen.

This pan-cancer analysis establishes APOC1 as a context-dependent biomarker and a TAM-derived modulator of adaptive immune resistance, with prognostic and therapeutic implications across malignancies. APOC1-expressing TAMs represent a potential target for combination immunotherapy strategies.

Entinostat-BPD achieved tumor-specific HDAC inhibition while displaying potent efficacy and reduced systemic toxicity. These findings reveal an HDAC-dependent DDR vulnerability and offer combinational and precision targeting strategies to facilitate clinical translation and improve PDAC patient outcomes.

Toripalimab combined with chemotherapy (Toripa-chemo) showed the greatest OS benefit in the overall population (HR = 0.58, 95% CI: 0.38-0.87). Atezolizumab combined with Entinostat and chemotherapy (Atezo-Entino-chemo) showed a trend toward improved OS (HR = 0.49, 95% CI: 0.22-1.12) and ORR (OR = 5.14, 95% CI: 0.70-37.94)...Toripa-chemo and Pembro-chemo demonstrate a balanced profile of efficacy and safety, suggesting that they may be suitable options for first-line treatment of mTNBC. Among these, Toripa-chemo may be considered a preferred first-line regimen for PD-L1 positive patients. https://www.crd.york.ac.uk/prospero/, identifier ID: CRD420251138714.

Consequently, investigators are testing checkpoint inhibitors in combination with drugs like the class I histone deacetylase inhibitor, entinostat (ENT)...However, by first "jump-starting" the T cell response using an oncolytic virus, the anti-tumor activity of ENT and PD1 blockade is restored. These data establish a general paradigm, independent of tumor type, to rationally manipulate anti-tumor immunity.

Pharmacologic inhibition of NUSAP1 with entinostat suppresses downstream target levels, suggesting a novel treatment modality. In summary, NUSAP1 promotes dedifferentiation through the BCAT1/α-KG/H3K27me3 axis by forming a transcriptional complex with BRD4, which indicates that NUSAP1 is a potential therapeutic target in TC.

The ability of tumor cells to tolerate DNA damage limits the efficacy of many anticancer therapies. Our study reveals that pancreatic cancer cells enforce this resistance by sustaining expression of DNA damage response (DDR) genes through Class I histone deacetylases (HDACs). HDACs maintain genome-wide acetylation patterns required for efficient recruitment of the transcriptional machinery to DDR genes. Pharmacological HDAC inhibition disrupts this process and sensitizes pancreatic cancer cells to diverse DNA-damaging agents. To overcome systemic toxicity that limits translational potential, we further establish a bottlebrush prodrug nanoparticle platform that enables tumor-selective HDAC inhibition. Given the central role of the DDR in cancer, targeting HDAC-mediated DDR regulation through drug combinations and precision delivery may have broad therapeutic relevance across cancer types.

Exploratory in silico drug-response analyses identified differential predicted responses to entinostat, linsitinib, and VE-822 according to risk status and DUBR expression. This internally validated signature may support exploratory prognostic risk stratification of LSCC within the analyzed TCGA-derived cohort and may highlight DUBR as a candidate molecule for further biological investigation. Further validation in independent external cohorts and dedicated disulfidptosis functional assays is required before these findings can be considered generalizable.

INPP4B, SLCO1B3, LIPH, TGM2, ACSL5, SLC2A1, and EPHX2 were identified as hypoxia- and lipid metabolism-related prognostic genes in PC. Distinct immune cell subsets were also characterized during PC progression. These findings provide a foundation for further mechanistic studies and potential prognostic applications.

Specifically, the high-risk group exhibited increased immune cell infiltration, lower IC50 values for several drugs including 5-fluorouracil, afatinib, crizotinib, cediranib, taselisib, and staurosporine; Whereas the low-risk group displayed reduced stromal component proportions and better responses to entinostat, irinotecan, KRAS inhibitors, cisplatin, axitinib, and topotecan. The lactylation-m6A related prognostic model exhibited robust predictive efficiency in HCC. TCOF1 and HDAC1 may be promising tumor biomarkers for HCC and more researches are needed to validate these results.

In vivo, we confirmed that entinostat treatment increased the expression of immunecheckpoint ligands and antigen presentation machinery in Myc-driven tumors in a Rb1/Trp53/MycT58A (RPM) SCLC mouse model, while shifting tumors from a neuroendocrine (NE)-high to a NE-low phenotype, and was associated with increased T-cell infiltration Notably, combining entinostat with anti-PD-1 immunotherapy suppresses tumor growth and significantly prolonged survival in RPM allograft models. These findings underscore the potential of entinostat to reprogram the NE status of SCLC, enhance immune checkpoint blockade efficacy, and improve therapeutic outcomes.

Comparative pathway analysis identified preferential de-repression of a G2/M checkpoint gene program in 105C spheroids upon Entinostat treatment when compared directly to the KOC-7c spheroids. Our results suggest that the utility of HDACi in OCCC is highly context-dependent.