barasertib-HQPA (AZD2811) / AstraZeneca, Pfizer - LARVOL DELTA

Aurora kinase B as a therapeutic target in HPV-induced cervical cancer: mechanisms and future perspectives. (PubMed, Front Oncol) - "Although clinical evaluation of these AURKB inhibitors such as barasertib (AZD1152) and AZD2811 remains limited, early findings support their potential efficacy, particularly in rationally designed combination regimens. This review describes the mechanistic interplay between HPV oncogenes and AURKB, highlights its role as a biomarker of aggressive disease, and critically assesses the therapeutic promise of AURKB inhibition. Finally, we outline future perspectives on integrating AURKB-targeted therapies into precision oncology for HPV-driven cervical cancer."

Journal • Review • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor • AURKB

Targeting AURKB Attenuates Tumor Growth in MYC-driven Lung Adenocarcinoma. (PubMed, Anticancer Res) - "AURKB contributes to LUAD progression by modulating MYC-driven oncogenic programs. Consequently, targeting the AURKB/MYC axis may represent a potential therapeutic strategy for MYC-dependent lung adenocarcinoma."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKB • CCNA2 • CDC20 • CDC45

Patient-derived organoids as a screening platform to identify mechanisms of osimertinib resistance in non-small cell lung cancer (AACR 2025) - "The c-MET inhibitor capmatinib was specifically potent in LPTO245 but not in other models. This finding was confirmed using savolitinib, another selective c-MET inhibitor, suggesting the observed effects were due to on-target c-MET inhibition...Additionally, we identified an inverse sensitivity correlation between osimertinib and the Aurora kinase B inhibitor AZD2811 across all 6 models (r = -0.64; p = 0.03)... Our screening platform can provide novel biological insights into osimertinib resistance. Moreover, it can potentially identify drug combinations with immediate clinical utility in NSCLC, particularly with approved and clinical-grade drugs."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AURKB • BRD4 • CDK4 • EGFR • PLK1 • ROS1

Aurora kinase B inhibition enhances radiation response and activates type 1 interferon signaling in triple-negative breast cancer (AACR 2026) - "Pharmacologic inhibition of AURKB using ATP-competitive (barasertib-HQPA) and noncompetitive (SP-96) compounds was evaluated in multiple human and murine TNBC cell lines... AURKB inhibition potentiates the efficacy of radiotherapy in TNBC by augmenting DNA damage and activating antitumoral T1IFN signaling. These findings identify AURKB as a dual radiosensitizing and immune-stimulatory target in TNBC, providing a strong rationale for clinical evaluation of AURKB inhibitors in combination with radiotherapy.References:1. Chandler BC, Moubadder L, Ritter CL, Liu M, Cameron M, Wilder-Romans K, et al."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKB • CXCL10 • IFNB1 • PD-L1

Proteomic evaluation of combination data in acute myeloid leukemia to inform mechanism of action and new targets (AACR 2024) - "In the proteomics evaluation study, MOLM13 cells treated for 7 days under different conditions - (1) vehicle control; (2) cytarabine alone; (3) decitabine alone; (4) venetoclax alone; (5) AZD4573 alone; (6) AZD4573+cytarabine; (7) AZD4573+decitabine; (8) AZD4573+venetoclax - were collected for proteomics analysis using LC-MS/MS...Interestingly, targeting AURKB with AZD2811 has been shown to overcome venetoclax resistance in AML... Our proteomics analysis identifies vulnerable and resistant pathways and proteins, shedding light on the mechanism of action and revealing potential new targets for AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AURKB • CDK9 • PHGDH

Molecular mechanism of S100P promotes hepatocellular carcinoma by regulating MYBL2-mediated transcription of AURKB. (PubMed, Cell Signal) - "HCC cells with low S100P expression showed significantly greater sensitivity to the AURKB inhibitor AZD1152-HQPA than control cells, with a 61% decrease in IC₅₀. This study reveals the S100P/MYBL2/AURKB axis as a key driver of HCC and a predictor of targeted therapy response, supporting precision treatment strategies."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • AURKB • MYBL2 • S100P

Targeting aurora kinase B (AURKB) as a radiosensitizing strategy in syngeneic models of triple negative breast cancer (TNBC) (AACR 2024) - "Here, we examined the effects of AURKB inhibition as a novel radiosensitizing strategy in syngeneic TNBC models. Cell viability assays were used to determine the half-maximal inhibitory concentrations (IC50) of the AURKB inhibitors Barasertib-HQPA and SP-96 72 hours post treatment... AURKB inhibition induces radiosensitization in syngeneic models of TNBC and leads to increased micronuclei and aneuploidy, suggesting a mechanism of sensitization. These results suggest that AURKB is a potential radiosensitizing strategy for the treatment of triple negative disease. Ongoing studies are further refining the underlying mechanisms of AURKB inhibition and RT on the antitumoral immune response."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKB

Potentiating antitumoral type 1 interferon immune signaling in triple-negative breast cancer (TNBC) via combination treatment of Aurora kinase B (AURKB) inhibition and radiation therapy (AACR 2025) - "Here, we examined the effects of combined RT and AURKB inhibition on T1IFN signaling in TNBC. The half-maximal inhibitory concentrations (IC50) were calculated using cell viability assays with the treatment of AURKB inhibitors Barasertib-HQPA and SP-96 in human and murine TNBC cells... AURKB inhibition and RT induces T1IFN signaling in human and murine TNBC cells. Combination treatment also induces micronuclei formation, suggesting an upstream mechanism for the observed T1IFN signaling. These data suggest that AURKB inhibition and RT may be a promising strategy for the treatment of TNBC and can modulate the tumor immune microenvironment."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKB • CXCL10 • IFNB1 • PD-L1

Treatment monitoring by biomarker analysis in a Phase I dose-expansion study of AZD2811 for relapsed/refractory small-cell lung cancer. (PubMed, Br J Cancer) - P1 | "A personalised surveillance strategy may provide a novel avenue to monitor SCLC, supporting further investigation and potential broader clinical application."

Biomarker • Journal • P1 data • Hematological Disorders • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • AURKB

TAZMAN: Study of AZD2811 + Durvalumab in ES-SCLC (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models. (PubMed, Genet Med) - "Our results implicate KLHL13-mediated AURKB regulation as a significant contributor to NDD in humans. Inhibiting AURKB activity could serve as a potential therapy to improve brain development and cognitive function."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Mental Retardation • Psychiatry • AURKB

Aurora B inhibition induces polyploidy and mitotic catastrophe in HER2-amplified breast cancer: Telomere shortening as a potential anticancer mechanism of AZD1152-HQPA. (PubMed, Biomed Pharmacother) - "Collectively, this study elucidates a novel anticancer mechanism associated with Aurora B inhibition, revealing that AZD1152-HQPA not only impairs mitotic fidelity and promotes polyploidization but also compromises the telomere/telomerase maintenance system. These findings highlight the therapeutic potential of Aurora B inhibitors in targeting telomere-associated vulnerabilities in polyploid cancer cells."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • TERT

Targeting aurkb mitigates colorectal cancer progression via kinase-independent regulation of PSAT1 (IDDF 2025) - "Subsequent experiments show that AURKB depletion reduces PSAT1 expression and serine biosynthesis, an effect not observed with the kinase inhibitor AZD2811, suggesting a kinase-independent mechanism (IDDF2025-ABS-0178 figure 3...PSAT1 rescues the proliferation suppression induced by AURKB depletion).Download figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0178 Figure 1 The expression pattern and prognostic significance of AURKB in CRCDownload figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0178 Figure 2 AURKB depletion inhibits CRC proliferation and induces apoptosisDownload figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0178 Figure 3 AURKB knockdown attenuates PSAT1 expression and serine biosynthesisDownload figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0178 Figure 4 AURKB inhibits HNRNPM-mediated PSAT1 mRNA degradationDownload figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0178..."

Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • AURKB • PSAT1

TAZMAN: Study of AZD2811 + Durvalumab in ES-SCLC (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2023 ➔ Dec 2025

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Co-inhibition of Aurora kinase B and SUV4-20H induces synthetic lethality in Wild-type p53 deficient cancer cells. (PubMed, Mol Cancer Ther) - "Barasertib (AZD2811) targets the mitotic kinase Aurora B (AURKB) and is in current clinical trials for various cancers. Lastly, we found in two different p53 mutated cell line tumor models that barasertib plus A196 has greater anti-tumor activity than either single agent. Our results suggest co-targeting of AURKB and SUV4-20H1/2 could be effective against p53-mutated or deficient cancers, including TNBCs in which approximately 80% of cases are p53 mutated."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKB • TP53

High-throughput screening identifies Aurora kinase B as a critical therapeutic target for Merkel cell carcinoma. (PubMed, Nat Commun) - "In mice, AZD2811 nanoparticles inhibit tumor growth and increase survival in both VP-MCC and VN-MCC xenograft models. Overall, our unbiased screens identify AURKB as a promising therapeutic target and AZD2811NP as a potential treatment for MCC."

Journal • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • AURKB

Unraveling the molecular landscape of non-small cell lung cancer: Integrating bioinformatics and statistical approaches to identify biomarkers and drug repurposing. (PubMed, Comput Biol Med) - "Finally, seven repurposed candidate drugs ENTRECTINIB, SORAFENIB, CHEMBL1765740, TOZASERTIB, NERVIANO, AZD-1152-HQPA, and SELICICLIB were proposed through molecular docking analysis. In conclusion, the findings of this study have the potential to significantly impact the early diagnosis, prognosis, and treatment of NSCLC."

Biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • CCNA2 • CCNB1

1H-19F cross-polarization magic angle spinning dynamic nuclear polarization NMR investigation of advanced pharmaceutical formulations. (PubMed, J Magn Reson) - "We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs)...The indirect 19F DNP enhancement εon/off(19F) = 26 was obtained via 1H-19F CP for the pure API impregnated with DNP solution, with an overall 30-fold sensitivity gain compared to the direct-detected 19F experiment under similar conditions. DNP enhancement value of εon/off(19F) = 42 was obtained via 1H-19F CP for the polymeric nanoparticle suspension and εon/off(19F) ≈ 150 were obtained for two different siRNAs in frozen DNP solution."

Journal

Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context. (PubMed, Neoplasia) - "We validated tumor suppressive activities of the AURKB inhibitor (AURKBi) Barasertib (AZD1152-HQPA) and the structurally unrelated compound GSK-1070916 in cerebellum slice culture models for SHH, and Grp3 MB...We revealed that the combination of AURKBi with the SRC/BCR-ABL inhibitor Dasatinib acts synergistically to repress tumor growth and expansion in the highly invasive MB cell model ONS-76, but not in Grp3 MB cells...In conclusion, we demonstrate that AURKB is essential for MB tumor growth and expansion in the tissue context and the inhibition of AURKB is equally efficient as irradiation in repressing tumor cell growth. In patients younger than three years, pharmacological targeting of AURKB may thus constitute a novel means to overcome radiotherapy limitations."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • ABL1 • AURKB • BCR

Differential regulation of expression of the protein kinases DYRK1A and DYRK1B in cancer cells. (PubMed, Sci Rep) - "Consistently, AURK inhibitors VX-680 (tozasertib), MLN8237 (alisertib), AZD1152-HQPA (barasertib) resulted in the upregulation of DYRK1B expression in A549 cells. In summary, our findings indicate that the expression of DYRK1A and DYRK1B is differentially regulated in cancer cells and reveal that the kinase inhibitor XMU-MP-1 increases DYRK1B expression likely through off target inhibition of Aurora kinases."

Journal • Oncology • AURKA • AURKB • DYRK1A • DYRK1B

Drug-induced senescence by aurora kinase inhibitors attenuates innate immune response of macrophages on gastric cancer organoids. (PubMed, Cancer Lett) - "It was found that DGCs showed drug-induced senescent phenotype after treatment by aurora kinases inhibitors (AURKi) Barasertib-HQPA and Danusertib. The up-regulation of local MCP-1/CCL2 can interact with MCP-1/CCL2 receptor (CCR2) expressed on macrophages and suppress their innate immunity to cancer cells. Overall, the special response of DGC to AURKi suggests that clinicians should select a sequential therapy with senescent cell clearance after AURKi treatment for DGC."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCL2 • CCR2

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3R-driven cells. (PubMed, Blood Cells Mol Dis) - "In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R mutation...Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL."

Journal • Chronic Neutrophilic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • ABL1 • AURKA • AURKB • CSF3R • STAT5

Targeting BCL2 overcomes resistance and augments response to aurora kinase B inhibition by AZD2811 in small cell lung cancer. (PubMed, Clin Cancer Res) - "BCL2 inhibition overcomes intrinsic resistance and enhances sensitivity to AURKB inhibition in SCLC preclinical models."

IO biomarker • Journal • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • AURKB • BCL2 • MYC

Targeting BCL2 overcomes resistance and augments response to aurora kinase B inhibition by AZD2811 in small cell lung cancer (Clin Cancer Res) - "AZD2811 showed potent growth inhibitory activity in a subset of SCLC, often characterized by, but not limited to, high cMYC expression....AZD2811-induced DNA damage and apoptosis were suppressed by high BCL2 levels, while combining AZD2811 with a BCL2 inhibitor significantly sensitized resistant models. In vivo, sustained tumor growth reduction and regression was achieved even with intermittent dosing of AZD2811 and venetoclax..."

Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Large scale pan cancer drug combination screening to identify effective and actionable combinations and biomarker hypothesis (AACR 2023) - "We selected 4 combinations based on clinical need and validated them further in vitro and in vivo (selumetinib plus venetoclax or AZD5991, AZD2811 plus venetoclax, and capivasertib plus AZD5991).To understand how molecular context affects drug response, we also used GDSC tools ANOVA to perform over 5.4 million statistical tests to identify statistically significant associations between drug response metrics and multi-omics features including mutations, CNAs, gene expression and methylation. This resulted in identification of 1,631 ‘emergent’ biomarkers.In summary, our screen and pipeline have been designed to optimize preclinical interpretation with a focus on actionability, particularly by our unique approach, and to provide a valuable resource for exploration by the wider research community. As a result of this screen, we identified and validated novel combination-tumor types in multiple cancer types."

Biomarker • IO biomarker • Pan tumor • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Endometrial Cancer • Oncology • Solid Tumor • AURKB • BRAF • KMT2D • KRAS • MLL2 • PIK3CA • PTEN • TP53