volasertib (NBL-001)

These research findings established silymarin as a potential alternative drug targeting PLK1, which is highly expressed in HER2-positive breast cancer, and modulates the oncogenic processes not just in breast cancer, but also in other cancers.

In vivo, volasertib treatment attenuated fibroblast activation and collagen deposition during TGFα-induced pulmonary fibrosis. Together, these findings identify a pathogenic role for the WT1-MYCN-PLK1 axis in fibroblast activation and provide proof-of-concept evidence supporting PLK1 inhibition with volasertib as a potential therapeutic strategy for IPF.

We evaluated cell cycle-targeted strategies to overcome HR-proficient chemoresistance using either volasertib (a selective PLK1 inhibitor) or adavosertib (a potent WEE1 inhibitor) in BRCA-WT/HR-proficient and BRCA-mutant/HR-deficient HGSOC models. Functional and xenograft models confirmed selective vulnerability of BRCA-WT tumors to either PLK1 or WEE1 inhibition. Our work highlights a mechanistic framework linking cell cycle checkpoint inhibition to DNA repair pathway selectivity, providing a rationale for targeting mitotic regulators in HR-proficient ovarian cancer-a subgroup with high clinical unmet need.

Here, a neutrophil/leukemia-tropic polymersome vincristine/volasertib dual-drug nanoformulation (NLP-Vi/Vo) is reported to selectively bind to leukemia cells and neutrophils, and to ratiometrically release clinical chemotherapeutics and a polo-like kinase 1 inhibitor, thereby potentiating the treatment of AML. NLP-Vi/Vo shows excellent therapeutic efficacy in malignant murine AML and human AML xenograft models. Collectively, neutrophil/leukemia-directing dual-drug nanomedicines offer a promising treatment strategy for AML.

Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype.

CDK4/6i-resistant cell lines (MCF7rR, MCF7rA, MCF7rP, T47DrR, T47DrA, and T47DrP) were isolated and evaluated for their aggressive phenotypes, cross-resistance, transcriptomic changes, and sensitivity to volasertib (PLK1 inhibitor) and barasertib (AukB inhibitor). We conclude that cell cycle upregulation leading to G2/M progression is a key route for CDK4/6i resistance. AukB or PLK1 inhibitors that block G2/M phase could be a promising strategy.

Tamoxifen (TAM) and adriamycin (ADM) served as positive control agents. HE staining demonstrated significant necrosis, while IHC/WB analysis validated that UA or UA combined with Volasertib may reduce levels of Bcl-2, PLK1, p-AKT/AKT, and p-mTOR/mTOR, in conjunction with increased LC3 II/I. In conclusion, the study revealed that UA may affect the apoptosis and autophagy of breast cancer through PLK1 via AKT/mTOR signaling pathway.

In this study, we aimed to decrease the dose of irradiation and the proliferation of MB by using Volasertib (VSB), a Polo-like kinase 1 (PLK1) specific inhibitor. Furthermore, COG133-LNPs along with irradiation decreased tumor burden significantly as compared to VSB or radiation alone. To our observation, COG133-LNPs display high potency in killing MB cells and sensitizing them toward radiation therapy.

Compared with free VCR/Vol, VCR/Vol polymersomes with tailored drug ratios substantially inhibited leukemia progression in both cell line- and patient-derived orthotopic ALL models without inducing toxicity, leading to a significant survival benefit. This synergistic polymersome injection may provide a powerful and safe combination therapy for ALL patients.

This causes the accumulation of DNA damage, ultimately leading to apoptotic cell death. Dual PLK1/MEK inhibition emerges as a promising targeted approach in PDAC.

Here, we evaluated the efficacy of the PLK1 inhibitor, volasertib, and the WEE1 inhibitor, adavosertib, along with the biomarker potential of cyclin E1 in ovarian cancer cells. Both inhibitors suppressed the growth of cyclin E1-overexpressing tumors in vivo. Taken together, cyclin E1 overexpression, regardless of TP53 status, may serve as a predictive biomarker for the efficacy of these inhibitors, offering potential personalized treatment strategies for ovarian cancer.

Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965).