- |||||||||| stenoparib (2X-121) / Allarity Therap, Oncoheroes
Biomarker, Phase classification: Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC (clinicaltrials.gov) - May 5, 2025
P1/2, N=166, Not yet recruiting,
Their ability to synergize with standard chemotherapy highlights their potential for clinical application. Phase classification: P2 --> P1/2
- |||||||||| dovitinib (TKI258) / Novartis, Oncoheroes, biapenem / Generic mfg., adefovir dipivoxil / Generic mfg.
FDA event, Journal: FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry. (Pubmed Central) - Apr 1, 2025
Phase classification: P2 --> P1/2 Pyridoxal 5'-phosphate, Dovitinib, Adefovir dipivoxil, and Biapenem potently inhibit ACE2-dependent viral entry with inhibitory concentration 50% (IC50) values of 57nM, 74
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
PLK1 inhibition as a novel therapeutic strategy in HER2+ breast cancer with germline METN375S mutation (Section 35; Poster Board No: 14) - Mar 25, 2025 - Abstract #AACR2025AACR_8992;
Our findings suggest that METN375S variant promotes tumorigenesis by hyperactivating HER2 signaling and enhancing PLK1 pathway. These findings highlight the potential of PLK1 inhibitors, as a novel therapeutic option for METN375S mutant HER2+ BC and supports further evaluation of PLK-1 in HER2+ BC.
- |||||||||| adavosertib (AZD1775) / AstraZeneca, volasertib (NBL-001) / Oncoheroes, Notable Labs
Cyclin E1 overexpression as a predictive biomarker for PLK1 and WEE1 inhibitor efficacy in ovarian cancer (Section 13; Poster Board No: 14) - Mar 25, 2025 - Abstract #AACR2025AACR_8293;
Both inhibitors induced cleaved PARP and ?H2AX in high Cyclin E1-expressing tumors but not in low-expression models. Cyclin E1 overexpression, regardless of TP53 status, may serve as a predictive biomarker for the efficacy of these inhibitors, thereby offering potential personalized treatment strategies for ovarian cancer.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Novel combinational therapeutic strategy in angiosarcoma through PLK1 and mTOR co-inhibition (Section 34; Poster Board No: 1) - Mar 25, 2025 - Abstract #AACR2025AACR_7761;
Our objective is to determine the mechanisms and pathways governing the development and progression of AS to generate novel precision-targeted therapies. Our findings conclude that PLK1 is a viable therapeutic target in AS, and the combined inhibition of PLK1 and mTOR represents a promising novel therapeutic strategy for this aggressive cancer.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, volasertib (NBL-001) / Oncoheroes, Notable Labs
Ovarian cancer treatments: Using HSF1 and MYC gene amplification as a biomarker (Section 16; Poster Board No: 19) - Mar 25, 2025 - Abstract #AACR2025AACR_6898;
We show that loss of HSF1 and MYC decrease proliferation and colony formation ability of ovarian cancer cells using knockdown siRNAs and that the Volasertib and Entinostat inhibitors are more effective in treating ovarian cancers that carry amplifications of HSF1 and MYC than those with other driver amplifications. Work with both Volasertib and Entinostat aim to show that amplifications of oncogenes in high-grade serous ovarian cancer can be used as a biomarker for new treatment strategies in ovarian cancer.
- |||||||||| dovitinib (TKI258) / Novartis, Oncoheroes
Journal: Identification of promising small-molecule inhibitors targeting STK17B for cancer therapeutics: molecular docking and molecular dynamics investigations. (Pubmed Central) - Feb 13, 2025
Ligand-based virtual screening and molecular docking were performed, resulting in the selection of three lead compounds (CID_135698391, CID_135453100, CID_136599608) with superior binding affinities compared to the reference compound dovitinib...Overall, small-molecule compounds CID_135453100 and CID_136599608 showed promising binding interactions and stability, suggesting their potential as direct inhibitors of STK17B. These findings could contribute to the exploration of novel therapeutic options targeting STK17B in cancer treatment.Communicated by Ramaswamy H. Sarma.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron, stenoparib (2X-121) / Allarity Therap, Oncoheroes
Journal, PARP Biomarker: GATA3-Driven ceRNA Network in Lung Adenocarcinoma Bone Metastasis Progression and Therapeutic Implications. (Pubmed Central) - Feb 13, 2025
These findings offer new insights into the molecular mechanisms of LUADBM and highlight potential therapeutic targets, including the XLOC_006941/miR-543/NPRL3 axis and GATA3-driven Th2 cell infiltration. The dual-target therapy combining E7449 with dupilumab shows promise for improving patient outcomes in LUADBM, warranting further clinical evaluation.
- |||||||||| stenoparib (2X-121) / Allarity Therap, Oncoheroes
Biomarker, Trial initiation date: Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC (clinicaltrials.gov) - Jan 28, 2025
P2, N=152, Not yet recruiting,
An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965). Initiation date: Jan 2025 --> Jun 2025
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, volasertib (NBL-001) / Oncoheroes, Notable Labs
Prediction of Volasertib Sensitivity in Acute Myeloid Leukemia Relapsed or Refractory to Venetoclax Plus Azacitidine () - Dec 7, 2024 - Abstract #ASH2024ASH_7898;
A randomized phase 2 trial in acute myeloid leukemia (AML) in the first line (1L) setting with the polo-like kinase 1 (PLK1) inhibitor volasertib (Vola) in combination with low-dose cytarabine (LDAC) yielded a 31.0% CR + CRi rate and a median overall survival (OS) of 8.0 months in contrast to 13.3% and 5.2 months, respectively, for LDAC without volasertib...Notable Labs has received US FDA clearance to test volasertib in combination with decitabine in a phase 2 clinical trial in relapsed/refractory (R/R) AML...Ven-refractory AML has no standard of care for treatment and portends dismal outcomes in patients. The encouraging performance of our ex vivo predictive medicine platform could pave the way for improving Vola response rates in patients in the upcoming phase 2 volasertib study.
- |||||||||| ispinesib (SB-715992) / Cytokinetics, alisertib (MLN8237) / Puma, volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence. (Pubmed Central) - Dec 6, 2024
Targeting STAT3 restores sensitivity to each of these drugs by depleting the senescent subpopulation and inducing quiescent cells to enter the mitotic cycle. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: NOD2 reduces the chemoresistance of melanoma by inhibiting the TYMS/PLK1 signaling axis. (Pubmed Central) - Oct 2, 2024
Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.
- |||||||||| Zarnestra (tipifarnib) / Kura Oncology, dovitinib (TKI258) / Novartis, Oncoheroes
Journal: Therapeutic Potental of Quinolin-2H-one Hybrids as Anticancer Agents. (Pubmed Central) - Sep 26, 2024
The current review presents information on the different quinolin-2-one hybrids and their effect on different cancer cell lines. It also imparts knowledge of the structural requirements for designing novel anticancer agents.
- |||||||||| dovitinib (TKI258) / Novartis, Oncoheroes, Rydapt (midostaurin) / Novartis
Journal, IO biomarker: Integrative alternative splicing analysis reveals new prognosis signature in B-cell acute lymphoblastic leukemia. (Pubmed Central) - Sep 9, 2024
More importantly, we conducted in vitro cell proliferation assays to confirm our analysis, demonstrating that the High-18AS cell line (SUP-B15) exhibited significantly enhanced sensitivity to Dasatinib, Dovitinib, and Midostaurin compared to the Low-18AS cell line (REH). These findings reveal AS events as novel prognostic biomarkers and therapeutic targets, advancing personalized treatment strategies in B-ALL management.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: MYC and HSF1 Cooperate to Drive PLK1 inhibitor Sensitivity in High Grade Serous Ovarian Cancer. (Pubmed Central) - Jun 25, 2024
Targeting PLK1 with the compound volasertib (BI-6727) revealed a greater than 200-fold increased potency of volasertib in HSF1-MYC co-amplified ovarian cancer cells compared to ovarian cancer cells wild-type HSF1 and MYC copy number, which extended to several growth assays, including spheroid growth. Volasertib, and other PLK1 inhibitors, have not shown great success in clinical trials and this study suggests that targeting PLK1 may be viable in a precision medicine approach using HSF1-MYC co-amplification as a biomarker for response.
- |||||||||| ispinesib (SB-715992) / Cytokinetics, alisertib (MLN8237) / Puma, volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: Resistance to Spindle Inhibitors in Glioblastoma Depends on STAT3 and Therapy Induced Senescence. (Pubmed Central) - Jun 19, 2024
Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Role of Polo-like kinase 1 in T2-low asthma model (PS-9; Poster board no. 5) - May 31, 2024 - Abstract #ERS2024ERS_436;
Application of PLK1-specific inhibitors volasertib significantly alleviated airway inflammation, airway remodeling (thickening of the airway smooth muscle layer and collagen deposition) and airway hyperresponsiveness... PLK1 is expected to be a potential target for the treatment of T2-low asthma by improving airway inflammation, airway remodeling and airway hyperresponsiveness.
- |||||||||| BI2536 / Boehringer Ingelheim, volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: PLK1 inhibition leads to mitotic arrest and triggers apoptosis in cholangiocarcinoma cells. (Pubmed Central) - May 29, 2024
Validation of the antiproliferative effects of PLK1 inhibition was accomplished through silencing of the PLK1 gene. In conclusion, targeting PLK1 provided promising results for further study as a potential candidate for targeted therapy in CCA.
- |||||||||| stenoparib (2X-121) / Allarity Therap, Oncoheroes
Enrollment closed, Trial completion date, Trial primary completion date, Metastases: PREDICT 2X-121: Investigation of 2X-121 in Patients With Advanced Ovarian Cancer Selected by the 2X-121 DRP (clinicaltrials.gov) - May 23, 2024
P2, N=60, Active, not recruiting,
In conclusion, targeting PLK1 provided promising results for further study as a potential candidate for targeted therapy in CCA. Recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Sep 2024
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells. (Pubmed Central) - Mar 27, 2024
In this study, we knocked down the Es-Kif2a gene by injecting dsRNA into E. sinensis and inhibited Es-Plk1 gene expression by injecting PLK1 inhibitor BI6727 into E. sinensis...Western Blot showed that the expression of Es-PLK1 decreased after Es-Kif2a knockdown, while there was no significant change of Es-KIF2A after Es-Plk1 inhibition, indicating that Es-PLK1 may be a downstream factor of Es-KIF2A. Taken together, these results suggest that Es-KIF2A upregulates the PI3K/AKT signaling pathway through Es-PLK1 during the spermatogenesis of E. sinensis, thereby affecting the proliferation and apoptosis levels of spermatogenic cells.
- |||||||||| Xalkori (crizotinib) / Pfizer, dovitinib (TKI258) / Allarity Therap, Oncoheroes
Biomarker, Journal: TBX15 and SDHB expression changes in colorectal cancer serve as potential prognostic biomarkers. (Pubmed Central) - Mar 22, 2024
Our findings highlight the potential association between alterations in the expression of genes such as HOXC6, HOXC13, HOXC8, TBX15, SDHB, COX5A, and UQCRC1 and increased mortality rates in CRC patients. As revealed by the PPI network, these genes exhibited the most connections with other genes linked to survival.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
PLK1 predicts aggressive behavior in CRC patients and its inhibition reverse chemoresistance in CRC cells (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_8044;
To explore the role of PLK1 on chemoresistance, we inhibited PLK1 using specific inhibitor, volasertib and we showed that volasertib effectively reversed 5-Fu resistance in these cells...In addition, we showed that silencing of ERK1/2 reversed the chemoresistance, EMT and stemness of PLK1 expressing CRC cell lines. Our findings underscore the significant role of PLK1 in conferring chemoresistance, and targeting PLK1 could represent a viable therapeutic approach for the treatment of patients with an aggressive subtype of CRC.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
VGLL1-derived peptides demonstrated anticancer effect by inhibiting VGLL1-TEAD4 interaction (Section 27) - Mar 5, 2024 - Abstract #AACR2024AACR_7961;
We also found that SCVP in combination and the PLK inhibitor volasertib resulted in a synergistic effect on the growth inhibition of breast cancer cells. In conclusion, we demonstrated VGLL1 as a novel target for anticancer drug development, and elucidated the molecular mechanism and therapeutic potential of the SCVP in gastric and breast cancers.
- |||||||||| thiostrepton (RSO-021) / RS Oncology, volasertib (NBL-001) / Oncoheroes, Notable Labs
The co-targeting of PLK1 and FoxM1 contributes to synergistic antitumor effects in PTC (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_6689;
The combined inhibition of PLK1 with volasertib and FoxM1 with thiostrepton synergistically attenuated PTC cell growth in vitro and in vivo. Our findings suggest that co-targeting of PLK1 and FoxM1 could be a viable therapeutic strategy for treating patients with an aggressive subtype of PTC.
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