alisertib (MLN8237) / Takeda, Puma - LARVOL DELTA

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

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

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

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

Alisertib and Barasertib Induce Cell Cycle Arrest and Mitochondria-Related Cell Death in Multiple Myeloma with Enhanced Efficacy Through Sequential Combination with BH3-Mimetics and Panobinostat. (PubMed, Cancers (Basel)) - "Alisertib and barasertib emerge as potential in vitro candidates against MM, although further studies are needed to validate their efficacy and to find the best combinations with other molecules."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CASP3

Cooperative Targeting of NF-κB Enhances Ferroptosis-Driven HCC Therapy with Alisertib and Donafenib (Frontiers) - "In vivo xenografts were established to evaluate the antitumor efficacy and potential side effects of the combination treatment, supported by histological and immunohistochemical analyses. Optimal synergistic concentrations (Alisertib 2.5 µM + Donafenib 10 µM for HCCLM3; 5 µM for Huh7) induced profound ferroptotic cascades, evidenced by elevated ROS, lipid peroxides, and Fe²⁺ accumulation concurrent with GSH depletion. The co-treatment potently inhibited p65 nuclear translocation while stabilizing IκBα, thereby suppressing NRF2-mediated antioxidant transcription. Xenograft models demonstrated marked tumor volume reduction with preserved organ architecture and hematological parameters, confirming clinical translatability.Alisertib is identified as a potent enhancer of Donafenib-induced ferroptosis through inhibition of the NF-κB/NRF2 pathway. This suggests a novel combinatorial strategy that targets ferroptosis through NF-κB inhibition."

Preclinical • Hepatocellular Cancer

Cellular senescence as a prognostic marker for predicting breast cancer progression in 2D and 3D organoid models. (PubMed, Biomed Pharmacother) - "To assess therapeutic potential, we treated cells and PDOs with Alisertib, an Aurora kinase inhibitor known to induce senescence...Overall, our results reveal a complex interplay between senescence and breast cancer progression. PAI-1 emerges as a functional effector of therapy-induced senescence and a promising candidate for further investigation as a diagnostic biomarker and potential target in senescence-based breast cancer therapies."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDKN1A

ALISCA-Lung1: A Study of Alisertib in Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Puma Biotechnology, Inc. | N=60 ➔ 80 | Trial completion date: Jan 2026 ➔ Oct 2027 | Trial primary completion date: Jul 2025 ➔ Apr 2027

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Aurora-A-mediated Maf1 phosphorylation plays a novel role by regulating mitochondrial function in hepatocellular carcinoma (EACR 2025) - "Alisertib was added to inhibit Aurora-A activity... Aurora-A promotes the protein stability and cytosolic localization of Maf1 via interacting with its C domain in a kinase-dependent manner in HCC cells. Aurora-A phosphorylation site mutant of Maf1 can promote nucleolar localization and lost the RNA polymerase III suppressor function and regulation of mitochondria. In Maf1 overexpressed HCC cells, Aurora-A inhibitor has a higher efficacy in inhibiting cell growth."

Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • MAF1 • PTEN

Targeting Aurora Kinase A in Breast Cancer Brain Metastasis (EACR 2025) - "In vivo, alisertib substantially reduced brain metastasis growth... Our findings establish AURKA as a critical vulnerability in BCBM. Targeting both its kinase-dependent and kinase-independent functions may offer new therapeutic strategies to improve patient outcomes."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKA • ER • HER-2

CRISPR-Cas9 mediated RALA knockout and reconstitution. Insights into the detection and role of RALA S194 phosphorylation in Ras-dependent and Ras-independent cancers. (PubMed, Biol Open) - "siRNA knockdown of RALA and AURKA inhibition by MLN8237 (VMLN) also did not affect pS194RALA detection in these cancers...Tumor growth was, however, restored partly by WT-RALA, but not S194A-RALA mutant. Thus, RALA S194 phosphorylation is needed for tumor formation, not affecting its activation, but possibly through its localization."

Journal • Oncology • RALA

Alisertib inhibits acute myeloid leukemia cell growth by inhibiting STAT3 activation. (PubMed, Toxicol Appl Pharmacol) - "In primary AML patient cells, we observed a consistent trend in the alisertib-induced reduction of pTyr705-STAT3 and cell growth inhibition. In conclusion AURKA and alisertib are promising therapeutic targets and treatment options for AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL6 • MYC • STAT3

ALISertib in combination with endocrine therapy in patients with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast cancer: The phase 2 ALISCA-Breast1 study. (ASCO 2025) - P2 | "Eligible pts will be randomized 1:1:1 to alisertib 30 mg, 40 mg, or 50 mg orally twice daily on days 1−3, 8–10, and 15–17 every 28 days, plus physician's choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in recurrent/metastatic setting or progressed upon in adjuvant setting; ≤50 pts will be enrolled per arm in the USA and Europe. Tumor tissue will be centrally assessed for biomarkers, including RB1, MYC, TP53, ESR1, PI3K/AKT pathway, HER2 and AURKA genomic alterations/expression levels. The study will determine the optimal alisertib dose to combine with ET and may identify biomarker(s) defining pts with the greatest benefit from alisertib-based therapy."

Clinical • Combination therapy • Metastases • P2 data • Anemia • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • ER • HER-2 • MYC • RB1

Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: M.D. Anderson Cancer Center | Terminated ➔ Completed

Trial completion • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Actionable heterogeneity of hepatocellular carcinoma therapy-induced senescence. (PubMed, Cancer Immunol Immunother) - "Interestingly, alisertib, etoposide and CX5461 rendered senescent HCC vulnerable to be targeted by either T-cell-engaging bispecific antibodies or CAR NK cells. Collectively, our study indicates that heterogenous, but selective features of HCC senescence may be exploited by different immunotherapeutic approaches."

Heterogeneity • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD276 • CD40 • FAS • HER-2

Predictive Oncology Reports First Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Announced that, using publicly available datasets on drugs that have either been abandoned or discontinued by large pharmaceutical companies, Predictive has developed a registry of promising candidates that can potentially be repurposed for additional or alternative indications. Predictive’s initial screening approach on a small, curated cohort of abandoned drugs identified three compounds that warrant further exploration in new colon and breast tumor indications. Specifically, Afuresertib (breast), Alisertib (colon) and Entinosta (colon) demonstrated the highest proportion of hits within those two tumor types." "

Clinical • Breast Cancer • Colon Cancer • Colorectal Cancer

Prognostic and immunological role of RHEBL1 in pan-cancer: a target for survival and immunotherapy. (PubMed, Discov Oncol) - "Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib."

IO biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CD8 • RHEB

Synergistic effects of Aurora A and AKT inhibitors combined with radiation in colon cancer cells. (PubMed, Discov Oncol) - "The integration of Aurora A and AKT inhibitors with radiation therapy synergistically enhances anticancer effects by amplifying DNA damage, disrupting mitotic progression, and inducing apoptosis. This combination represents a promising strategy for overcoming treatment resistance in colon cancer."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

ALISCA-Breast1: A phase II study of ALISertib in combination with endocrine therapy in patients with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast CAncer (ESMO-BC 2025) - P2 | "Eligible patients are randomized 1:1:1 to alisertib 30, 40, or 50 mg orally bid on d1−3, 8–10, and 15–17 q28d, plus physician's choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in recurrent/metastatic setting or progressed upon in adjuvant setting; up to 50 patients will be randomized per arm in the USA and Europe. All biomarkers will be assessed centrally. The study will determine the optimal alisertib dose to combine with ET."

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Targeting EMT-driven metastatic breast cancer with mitotic inhibitors (ESMO-BC 2025) - "These findings highlight the therapeutic potential of AURKA inhibitors for targeting hybrid EMT states present in CTCs and invasive regions of primary tumors, offering a strategy to combat metastatic disease and potentially transform current breast cancer treatment."

Metastases • Breast Cancer • Oncology • Solid Tumor • CDH1 • CDH2 • CTCs • FN1 • SNAI1 • VIM • ZEB1

Puma Biotechnology Reports First 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 (H2 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 (H2 2025)."

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

O 6-methylguanine DNA methyltransferase (MGMT) expression in U1242 glioblastoma cells enhances in vitro clonogenicity, tumor implantation in vivo, and sensitivity to alisertib-carboplatin combination treatment. (PubMed, Front Cell Neurosci) - "The action of the widely used antiglioma drug, temozolomide (TMZ), relies on its ability to methylate DNA guanine bases leading to DNA double strand breaks and apoptosis. We additionally show that the combination of the AURKA inhibitor alisertib and carboplatin selectively induces apoptosis in high MGMT expressing wildtype U1242 cells versus MGMT KO U1242 cells and extends survival of mice orthotopically implanted with wildtype U1242 cells. This or other platinum-based drug combinations may represent a potentially effective treatment approach to chemotherapy for GBM with MGMT promoter hypomethylation."

Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • MGMT

Alisertib impairs the stemness of hepatocellular carcinoma by inhibiting purine synthesis. (PubMed, J Biol Chem) - "This disruption markedly impaired tumor spheroid formation, migration, and invasion in vitro, while significantly suppressing tumor growth in vivo-effects reversible by the AKT agonist SC79. Our findings revealed a novel therapeutic strategy targeting purine metabolism through AURKA/AKT axis inhibition, effectively eliminating HCC-TRCs."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor