alisertib (MLN8237) / Takeda, Puma - LARVOL DELTA

The Aurora Kinase A Inhibitor Alisertib Alone or in Combination with Endocrine Therapy for Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Metastatic Breast Cancer (MBC) (SABCS 2025) - "Abstract is embargoed at this time."

Clinical • Combination therapy • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AURKA • ER • HER-2

Puma Biotechnology Reports Third Quarter 2025 Financial Results (Businesswire) - "We anticipate the following key milestones over the next 12 months: (i) presentation of interim data from ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (H1 2026) and (ii) presentation of additional interim data from the ALI-4201/ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (H1 2026)."

P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Small Cell Lung Cancer

A Phase 2 study of alisertib in combination therapy for newly diagnosed Atypical Teratoid/Rhabdoid Tumor (AT/RT)- Results from SJATRT strata B and C (WFNOS 2025) - "Combination of alisertib with chemotherapy and RT was well tolerated, however, it didn't improve survival in newly diagnosed AT/RT. The study confirms, albeit in small numbers, prior results of a higher survival for M0 patients with post-operative CSI in > 36-month-old (C1). The PFS in M+ > 36-month-old patients (C2) was higher with CSI than previously reported."

Combination therapy • P2 data • Brain Cancer • Oncology • Pediatrics • Rhabdoid Tumor • Sarcoma • Solid Tumor • AURKA • SMARCA4 • SMARCB1

Aurora Kinase A inhibitor alisertib failed to exert its efficacy on TNBC cells due to consequential enrichment of polyploid giant cancer cells (PGCCs). (PubMed, Discov Oncol) - "PGCCs contributed to alisertib insensitivity in TNBCs that may be targeted by mifepristone."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKA

FEDRATINIB TARGETING AURKA AND THE JAK2/STAT3 PATHWAY TO SUPPRESS TUMOR PROGRESSION IN RHABDOMYOSARCOMA (SIOP 2025) - "Fedratinib exerted an anti-RMS effect via inhibiting AURKA and the JAK2/STAT3 signaling pathway, it also sensitized the AURKA inhibitor Alisertib when used in combination."

Myelofibrosis • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • AURKA

WSB1-Mediated Degradation of PSMA Drives Neuroendocrine Differentiation in Early Prostate Cancer (AACR-NCI-EORTC 2025) - "Using patient-derived 3D spheroid cultures established from seven treatment-naïve prostate cancer biopsies, we modeled prolonged exposure to enzalutamide or abiraterone and observed progressive loss of prostate-specific membrane antigen (PSMA/FOLH1) accompanied by increased expression of neuroendocrine markers chromogranin A and synaptophysin...Consistent with this finding, t-NEPC spheroids derived from long-term drug-exposed patient samples exhibited pronounced sensitivity to the Aurora A inhibitors alisertib and ENMD-2076, independent of WSB1 expression levels but associated with impaired WSB1 E3 ligase activation...Targeting WSB1-dependent degradation pathways, either directly or through upstream Aurora A inhibition, may provide a rational therapeutic strategy to suppress or delay the emergence of t-NEPC in patients receiving AR-directed therapies. *These results were obtained after the regular abstract submission deadline and represent newly generated..."

Late-breaking abstract • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • AURKA • CHGA • FOLH1 • KLK3 • SYP • WSB1

A chemical probe designed to capture MET reveals Aurora kinase A but not MET expression as the primary target for sensitizing cells to paclitaxel (AACR-NCI-EORTC 2025) - "Within this context, we designed a new probe with a crizotinib warhead, and a PEG linker attached to a biotin moiety, with the purpose of targeting MET and other off-target kinases...Using AB19 under conditions where cancer cells were treated with paclitaxel for 2 and 24 h led to kinase binding profiles wherein MET was the primary target... The results in toto suggest that despite being targeted to MET expression, the probe can reveal expression of other kinases that could be targeted for synergistic combinations with standard-of-care drugs. Further studies are ongoing to correlate the probe captures with more protein expression analyses in brain and lung cancer cell lines."

Late-breaking abstract • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • AURKA • MET

BUILDING THE FOUNDATION TO OPTIMIZE UTILIZATION OF ALISERTIB IN HIGH GRADE SEROUS CARCINOMA (IGCS 2025) - "CBX2 knockdown reduced tumor weights and the number of dissemination sites (p < 0.05). Alisertib similarly reduced tumor burden (p < 0.0001); however, this effect depended on the presence of CBX2 (Fig1). Tumor weights and number of dissemination sites were similar in vehicle- and alisertib-treated shCbx2 mice."

Oncology • AURKA • BRCA2 • CBX2

Overexpression of the TPX2 gene is associated with enhanced tumor malignancy in lung adenocarcinoma and identification of marine natural inhibitors of the Aurora kinase A-TPX2 protein complex. (PubMed, In Silico Pharmacol) - "The MD over 200 ns indicated that marine compounds, such as Shellmycin C (CID:156581889) and Rhodoptilometrin (CID:625242), displayed significantly greater stability compared to the control drug Alisertib (CID:24771867). Consequently, these findings underscore the potential for developing innovative therapeutic strategies that target the AURKA-TPX2 complex in LUAD, warranting further validation through in vitro and in vivo studies. The online version contains supplementary material available at 10.1007/s40203-025-00436-z."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • TPX2

Survivin and Aurora Kinase A control cell fate decisions during mitosis. (PubMed, Mol Oncol) - "Alisertib enables both normal and transformed cells with high levels of survivin to activate the APC/C prematurely, as observed by the destruction of cyclin B and securin. Thus, a high expression of survivin can alter cell fate decisions at mitosis and lead to genetic instability, a key hallmark in cancer."

Journal • Oncology • AURKA • AURKB • BIRC5 • BUB1B

Inhibition of Mitotic Aurora Kinase A by Alisertib Induces Apoptosis and Autophagy of Human Gastric Cancer AGS and NCI-N78 Cells [Retraction]. (PubMed, Drug Des Devel Ther) - "[This retracts the article DOI: 10.2147/DDDT.S74127.]."

Journal • Gastric Cancer • Oncology • Solid Tumor • AURKA

The Investigational Aurora Kinase A Inhibitor Alisertib (MLN8237) Induces Cell Cycle G2/M Arrest, Apoptosis, and Autophagy via p38 MAPK and Akt/mTOR Signaling Pathways in Human Breast Cancer Cells [Retraction]. (PubMed, Drug Des Devel Ther) - "[This retracts the article DOI: 10.2147/DDDT.S75378.]."

Journal • Breast Cancer • Oncology • Solid Tumor • AURKA

Puma Awaits Key Lung And Breast Cancer Trial Data For Aurora Kinase A Inhibitor... (RTTNews) - "The interim data from the ALISCA-Breast1 trial is anticipated between Q4 2025 and the first half of 2026...The company expects to present additional interim data from the ALISCA-Lung1 trial in the fourth quarter of 2025."

P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Small Cell Lung Cancer

Anti-cancer compound screening identifies Aurora Kinase A inhibition as a means to favor CRISPR/Cas9 gene correction over knock-out. (PubMed, PLoS One) - "Three were shown to be beneficial after validation: rucaparib, belinostat and alisertib. The Aurora Kinase A inhibitor alisertib in particular led to an over 4-fold increase in preferential gene correction over gene knock-out in two cell models (HEK293T and Hepa 1-6) at sub-micromolar dosages on the eGFP locus, prompting further validation. On the long term this pathway did show cytotoxicity especially in the HEK293T cells, indicating further mechanistic investigation is needed, but this toxicity was less pronounced in primary hepatocytes."

Journal • Gene Therapies • Genetic Disorders • Oncology • AURKA

Differentially Expressed Genes and Biological Pathways in Moyamoya Disease: A Systematic Review and Meta-analysis of Transcriptomic Studies. (PubMed, Transl Stroke Res) - "Gene-drug interaction analysis highlighted MI-773 and MLN 8237 as potential MMD therapy. This study identifies distinct biological pathways that are dysregulated in key tissues of MMD patients. Given the current limited treatment options for MMD, our findings offer potential biomarkers for risk stratification and novel therapeutic targets that could pave the way for improved management of this debilitating disease."

Journal • Retrospective data • Review • Cardiovascular • CNS Disorders • Vascular Neurology • BDNF

Aurora kinase A inhibition as a synthetic lethality strategy in ARID1A-mutated gastroenteropancreatic neuroendocrine carcinoma. (PubMed, Cancer Lett) - "Chemotherapy with cisplatin (CDDP) and etoposide (ETO) is the standard treatment for gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)...Here, we evaluated Aurora kinase inhibition with alisertib (ALI) as a synthetic lethality strategy in ARID1A-deficient GEP-NEC...These findings establish Aurora kinase inhibition as mechanistically distinct and selectively effective in ARID1A-deficient GEP-NEC. Given its efficacy, favorable tolerability, and ARID1A-dependent specificity, ALI may represent a promising alternative to platinum-based chemotherapy, offering a strong rationale for further development of mechanism-driven combination strategies for GEP-NEC."

Journal • Endocrine Cancer • Gastrointestinal Neuroendocrine Carcinoma • Metabolic Disorders • Neuroendocrine Carcinoma • Oncology • Pancreatic Cancer • Solid Tumor • ARID1A • AURKA

Epigenetic Regulation of OLIG2 in Glioblastoma: Mechanisms and Therapeutic Targets to Combat Treatment Resistance. (PubMed, J Mol Neurosci) - "Additionally, this paper highlights the potential of combination therapies targeting multiple epigenetic pathways simultaneously. A kinase inhibitor (alisertib), together with JQ1, reduced the tumor growth of GBM cells in vivo more than either treatment alone, making combination therapies a promising solution."

Journal • Review • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • DNMT1 • HDAC2 • KDM6B • MIR17 • OLIG2 • SMARCA4

Discovery of Potent and Selective Pyrrolo[2,3-d]Pyrimidine-Based Aurora A Inhibitors with Demonstrated Efficacy against Patient-Derived Gastric Cancer Organoids. (PubMed, J Med Chem) - "It also exhibited strong antiproliferative effects in gastric cancer cell lines and superior efficacy in patient-derived gastric cancer organoids (IC50 = 3.5 μM), outperforming Alisertib. These findings suggest that compound 11 is a highly potent and selective Aurora A inhibitor with significant therapeutic potential for gastric cancer treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • AURKA

Aurora-A inhibits hepatocellular carcinoma cell ferroptosis to mediate immune escape by disrupting phosphatidylethanolamine biosynthesis. (PubMed, Am J Cancer Res) - "Further, Aurora-A inhibitor Alisertib enhanced the sensibility of HCC cells to anti-PD-1 therapy and CD45+CD8+ T cell infiltration in HCC tumors. To conclude, our work revealed that Aurora-A dysregulated PS/PE metabolism via facilitating Drp1-Ser616 phosphorylation to disrupt MAMs formation, resulting in suppressed ferroptosis in HCC cells to reduce their sensitivity to anti-PD-1."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • PTPRC

The AURKA-Selective Inhibitor Alisertib Attenuates Doxorubicin-Induced Hepatotoxicity in Mice via Modulation of IL-17A/NF-κB and STAT3 Signaling Pathways. (PubMed, Pharmaceuticals (Basel)) - "These beneficial effects of alisertib were further reflected in the histopathological findings, which indicated the ability of alisertib to ameliorate DOXO-induced hepatic necroinflammation and fibrosis. Alisertib mitigates DOXO-induced hepatotoxicity in mice via targeting the IL-17A/NF-κB and IL-17A/STAT3/HIF-1α/VEGF-A signaling pathways, attenuating oxidative stress, inflammation, ER stress, and fibrosis."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Oncology • AURKA • HIF1A • IL17A • TGFB1

Cooperative targeting of NF-κB enhances ferroptosis-driven HCC therapy with Alisertib and Donafenib. (PubMed, Front Cell Dev Biol) - "This suggests a novel combinatorial strategy that targets ferroptosis through NF-κB inhibition. Further research is needed to translate these promising results into clinical practice."

Journal • Hematological Disorders • Hepatocellular Cancer • Oncology • Solid Tumor • AURKA • NFKBIA

Safety of alisertib in the treatment of solid and hematological cancers: A systematic review and meta-analysis of randomized controlled trials. (PubMed, J Oncol Pharm Pract) - "Hematologic toxicities, including anemia, febrile neutropenia, neutropenia, and leukopenia, were markedly increased with alisertib. Similarly, gastrointestinal AEs, particularly diarrhea, were more frequent in the alisertib group.ConclusionAlisertib significantly increases the risk of hematologic and gastrointestinal toxicities compared to chemotherapy, highlighting the need for careful monitoring and a thorough benefit-risk assessment."

Journal • Retrospective data • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukopenia • Neutropenia • Oncology • Solid Tumor • AURKA

Aurora kinase A drives non-canonical YAP1/TAZ crosstalk to sustain primary resistance to anti-EGFR therapies in colorectal cancer. (PubMed, Mol Ther Oncol) - "By integrating preclinical in vitro and in vivo models, including cell lines and patient-derived xenografts, with RNA sequencing, we investigated the impact of TAZ overexpression in cetuximab resistance driven by the AURKA/YAP1 axis...Treatment with alisertib, a phase III AURKA inhibitor, simultaneously destabilizes YAP1 and TAZ, restoring anti-EGFR efficacy by suppressing stemness. Transcriptomic analyses further show that AURKA inhibition and dual YAP1/TAZ suppression disrupt stem-like traits and reveal transcriptional deregulations affecting nucleotide metabolism. These findings demonstrate that AURKA orchestrates YAP1/TAZ crosstalk, which is crucial for driving stemness and resistance to anti-EGFR therapies, highlighting AURKA inhibitors as a promising strategy to enhance anti-EGFR therapies in metastatic CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • AURKA • TAFAZZIN • YAP1

Puma Biotechnology Reports Second Quarter Financial Results (Businesswire) - "...'We anticipate the following key milestones over the next 12 months: (i) presentation of interim data from ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (Q4 2025) and (ii) presentation of additional interim data from the ALI-4201/ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (Q4 2025)'."

P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Small Cell Lung Cancer

Unimolecular Micelle for MLN8237 Delivery to Target AURKA-RalA Crosstalk for Ras-Driven Tumor Suppression in Mice Xenografts. (PubMed, Biomacromolecules) - "This correlated with inhibition of AURKA and RalA phosphorylation (pSer194RalA) in both tumors. Together, they highlight the therapeutic potential of NPMLN in targeting AURKA-RalA crosstalk in tumor xenografts."

Journal • Preclinical • Oncology • AURKA • RALA