B9 exhibited low nanomolar enzymatic inhibition and exceptional cellular potency (IC50 = 0.4 nM in K562 leukemia cells), representing a >150-fold improvement over the reversible reference compound BI2536 (61 nM)...In an orthotopic K562 leukemia xenograft model, oral administration of B9 significantly suppressed the bioluminescence of leukemia burden and extended survival rates to 100% over 42 days without observable toxicity. These findings underscore the potential of B9 as a safe, orally bioavailable, and highly potent PLK1 inhibitor for preclinical development.

Pharmacologic inhibition of PLK1 with volasertib significantly suppressed tumor growth in both syngeneic and autochthonous mouse models. Moreover, combining PLK1 inhibition with anti-PD-1 therapy enhanced tumor control and improved survival compared with either treatment alone. Together, these results identify PLK1 as a potential therapeutic vulnerability in BAP1-deficient sarcomas and support further evaluation of combined PLK1 inhibition and immune checkpoint blockade as a treatment strategy for a subset of STS.

Importantly, synchronizing Bi2536 administration with the circadian peaks of PLK1 expression further augmented its therapeutic efficacy. In summary, our work establishes that the combination of Bi2536 with a biomimetic nano-delivery system, together with its chronotherapeutic administration, constitutes a highly promising and multifaceted strategy for the treatment of HGSOC.

Drug sensitivity analysis revealed differential responses to 4 drugs between the risk groups, with the 3 ORGs (ACSS2, CLTCL1 and PLD3) showing positive correlations with 2 drugs (BI_2536, Dactinomycin). Additionally, functional experiments confirmed the role of ACSS2 in OS cell behavior. This novel ORG signature not only provides a valuable tool for patient stratification but also offers insights into the biological processes driving OS progression and potential therapeutic targets.

Herein, we report a chemoimmunotherapeutic fibrin sealant (CI-sealant) as a new postsurgical adjuvant therapy that converts the surgical cavity into an in situ "drug-immune depot" with localized release of immunogenic docetaxel/volasertib dual-drug nanocombo (iNCombo) and galunisertib, a TGF-β inhibitor that relieves immune suppression. Post-surgery adjuvant therapy with CI-sealant significantly prevents tumor recurrence in both murine 4 T1-Luc breast tumor and B16F10 melanoma models. This chemoimmunotherapeutic sealant opens a promising strategy for postsurgical adjuvant therapy of malignant tumors.

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.

P2, N=7, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Suspended --> Active, not recruiting | N=29 --> 7

The 90% ethanol-aqueous extract of C. asiatica whole plant, which was prepared at room temperature, contained ten bioactive compounds including rutin, quercetin, kaempferol, chlorogenic acid, fisetin, apigenin, asiatic acid, fumaric acid, betulinic acid and ursolic acid identified by UHPLC method. As our findings, rutin was identified as a promising PLK-1 inhibitor that exhibited significant docking score -13.07 and high stability within the binding pockets of PLK-1 protein as compared to control drug onvansertib. Furthermore, experimental validation is urgently needed for future translational research to develop rutin as potent PLK-1 inhibitor for treating cancer.

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.

P1, N=260, Recruiting, SillaJen, Inc. | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Dec 2026

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.

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.