Proteomic analysis identified unique protein candidates altered in MZ-1- and SIM-1-treated KSHV-infected immortalized endothelial cells compared with (+)-JQ1-treated cells. In summary, our study develops an effective strategy against KSHV-infected immortalized endothelial cells using selective BRD PROTACs, which may help improve therapeutic outcomes for KSHV-related malignancies in the future.

Patients in the high‑risk group showed improved responses to lapatinib, BI‑2536, OSI‑027, and SB505124, whereas those in the low‑risk subgroup had better sensitivity to axitinib, epirubicin, fulvestrant, and olaparib. Additionally, CD24 overexpression in BC cell lines promoted proliferation and migration, and inhibited apoptosis. These findings contribute to personalized treatment strategies and help elucidate the tumor microenvironment characteristics of BC patients.

We establish NNMT as a central metabolic-immune hub that orchestrates TGF-β-mediated CD8⁺ T cell dysfunction and endothelial reprogramming in ccRCC.

Leveraging insights from the BRD4 inhibitor Y-803, we has developed MT-4561, which demonstrates high degradation activity and antitumor efficacy and is currently in Phase I clinical trials. These efforts exemplify a modality-driven drug discovery approach tailored to disease-specific pathologies, aiming to provide new therapeutic options for intractable diseases through the integration of scientific knowledge and technological innovation.

There were 61 drugs with significant differences in IC50 between the high and low risk groups, such as BI.2536 and PD-173074...We identified three prognostic genes associated with efferocytosis in HCC and integrated them into a risk prognostic model. These genes not only serve as signatures for predicting HCC prognosis but also offer insights into the treatment of HCC.

Our predictive model offers a novel perspective on the stemness landscape of TNBC. These core genes play key roles in maintaining stemness and also serve as potential molecular targets for personalized therapies aimed at TNBC stem-like cells.

Further molecular mechanism study revealed that AZD5153 inhibited radiotherapy-activated ATM-chk1 pathway, suggesting that AZD5153 may enhance radiosensitivity by impairing DNA damage repair. Collectively, these results suggested that AZD5153 might be a promising radiosensitizing agent, and targeting the ATM-chk1 pathway may offer a novel therapeutic strategy to overcome radioresistance in pancreatic cancer.

Through bioinformatics analysis, it was discovered that DLX5 exerts an oncogenic role in HPSCC through co-amplification with TP63 and activation of the MAPK signaling pathway, with functional assays further confirming its promotion of malignant phenotypes. High expression of DLX5 correlates positively with immunosuppressive cells, such as M2 macrophages, and negatively with antitumor CD8+ T cells, indicating an association with an immunosuppressive microenvironment. These findings highlight DLX5 as a key determinant of poor prognosis in HPSCC.

BI-2536 in combination with β-glucan exhibits synergistic anticancer effects in vitro, suggesting a promising strategy for treating colon and gastric cancers.

We discovered bromodomain-containing protein 4 (BRD4) degraders as novel antitumor therapeutics leveraging our internal knowledge on Y-803 (birabresib, OTX015/MK-8628), which was discovered by our company as the first-in-class BRD4 inhibitor. Since we had obtained rich structure-activity relationship (SAR) information on its core skeleton, thienodiazepine, we designed and optimized Von Hippel-Lindau (VHL)-based BRD4 degraders based on the thienodiazepine scaffold. Here, we report that we obtained a novel, best-in-class BRD4 degrader, which showed a potent antitumor effect in a xenograft model of acute myeloid leukemia (AML).

Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLL1-r AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1-r or mtNPM1.

Here, we develop a novel ISTV platform (SOM-ZIF-8@Mn/ARV) integrating a specific ICD inducer (ARV-825), and a multifunctional antigen catcher (SOM-ZIF-8@Mn) to boost antitumor immunity...This ISTV platform triggers robust antitumor immunity and achieves significant tumor growth inhibition when combined with αPD-1 blockade. The SOM-ZIF-8@Mn/ARV platform represents a powerful and effective advancement in improving the antitumor immune efficiency of ISTVs, offering a straightforward approach to the challenges faced in tumor immunotherapy.