alisertib (MLN8237) / Takeda, Puma - LARVOL DELTA

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

Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer (clinicaltrials.gov) - P1/2 | N=24 | Terminated | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Terminated; <75% participation accrual

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

Pharmacological blockade of AURKA and NOTCH3 oncogenic pathways to inhibit cancer cell plasticity in triple negative breast cancer (AACR 2025) - "TNBC cells were treated with Alisertib (AURKA inhibitor, 50nM) or AV353 (NOTCH3 inhibitor, 200ng). This study demonstrates that selective AURKA and NOTCH3 pharmacological blockade results in the inhibition of cancer cell plasticity that is linked to reduction of undruggable nuclear PD-L1 in TNBC cells. Our findings provide the strong preclinical rationale to develop novel clinical trials for patients with advanced TNBC that are refractory to chemotherapy and show limited response to FDA-approved ICIs."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKA • CD44 • CD8 • NOTCH3

Therapy-induced senescence promotes tumor immunosuppression in cholangiocarcinoma (AACR 2025) - "Mice were treated for two weeks with the potent senescence inducers, alisertib, etoposide, or doxorubicin...Both p16+ and p21+ cancer cells were increased in tumors from patients who have undergone cytotoxic therapy with gemcitabine/cisplatin (Gem/Cis)... we have demonstrated that senescent cancer cells accumulate in tumors from patients treated with standard-of-care therapy with Gem/Cis. Senescent cancer cells enhance the abundance and suppressive function of MDSCs via TRAIL. Thus, senolysis has the potential to rewire the TIME, and augment response to systemic therapy."

IO biomarker • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CD8 • CDKN1A • CDKN2A

Aurora-A inhibition sensitizes HPV-driven cancers to anti-CTLA-4 immunotherapy by modulating the tumor immune microenvironment (AACR 2025) - "Alisertib (Ali), an Aurora kinase A inhibitor, may sensitize these cancers to ICIs by inducing apoptosis and DNA damage...RNA-seq analysis shows that Ali drives immune responses, further amplified by anti-CTLA-4, promoting both immune and metabolic reprogramming. These findings suggest that combining Ali with ICI could overcome resistance and improve therapeutic outcomes in HPV-positive cancers."

IO biomarker • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • AURKA • CASP3 • CD4 • CD8 • IFNG • LAG3

A novel class of multitarget small molecule PI3K-CDK4/6-CDK9-AURAKA/B inhibitor harnesses Warburg effect against non-small cell lung cancer (AACR 2025) - "Here, we describe how LCI139 harnesses the Warburg effect to induce synthetic lethality in NSCLC. LCI139-sensitive (NCI-H1703) and resistant (NCI-H1781) human NSCLC cells, identified from prior IC50 experiments, were treated with LCI139 (0.25 and 0.5μM) or single agent inhibitors PI3Ki (BKM120), CDK4/6i (Ribociclib), CDK9i (AZD4573), and AURKAi (Alisertib). Multitarget inhibitor, LCI139 is uniquely designed to harness the Warburg effect to induce synthetic lethality in glycolysis-reliant NSCLC by 1) inducing metabolic stress (pAMPK), 2) lowering the threshold to metabolic stress response (FoxO3 stabilization), and 3) enhancing caspase-dependent cell death non-canonical Cas8 activation."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • BAX • BCL2 • BCL2L11 • CDK9 • SLC2A1

Exploiting Rb-deficiency: Dual inhibition of TRIP13 and Aurora A as a path to mitotic catastrophe (AACR 2025) - "Our previous research demonstrated that the combination of Aurora A inhibition using specific inhibitor alisertib and TRIP13 depletion induced synthetic lethality selectively in Rb-deficient cancer cells where the combination induced mitotic catastrophe...This is the first study to elucidate the mechanism behind the synthetic lethality of TRIP13 and Aurora A in Rb-deficient cancer cells. These findings may provide important insight into how to rationally design novel therapeutic strategies targeting mitotic regulators by harnessing the therapeutic vulnerability of Rb-deficient cancer cells."

Oncology • Solid Tumor • AURKA • CDK1 • GSDME • TRIP13

Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine. (PubMed, iScience) - "In liver orthotopic tumor models, the combination of pGPC3 vaccine and alisertib demonstrated potent therapeutic efficacy through CD8+ T cell responses. These results indicate that alisertib enhances the pGPC3 vaccine's therapeutic effect, offering a promising strategy for HCC treatment."

Journal • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKA • ITGAX

ALISertib in Combination With Endocrine Therapy in Patients With Hormone Receptor-Positive, HER2-Negative Recurrent or Metastatic Breast Cancer: the Phase 2 ALISCA-Breast1 Study (MBCC 2025) - P2 | "Eligible patients will be randomized 1:1:1 to alisertib 30 mg, 40 mg, or 50 mg orally twice daily on days 1 to 3, 8 to 10, and 15 to 17 every 28 days and combined with physician's choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in the recurrent or metastatic setting or progressed upon in the adjuvant setting. Tumor tissue will be centrally assessed for biomarkers, including but not limited to RB1, MYC, TP53, ESR1, PI3K/AKT pathway, HER2, and AURKA genomic alterations and/or expression levels. The study is expected to determine the optimal alisertib dose to combine with ET and may identify biomarker(s) that define patients deriving the greatest benefit from alisertib-containing therapy."

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