alisertib (MLN8237) / Takeda, Puma - LARVOL DELTA

Chromobox2 inhibition: a novel activity of alisertib, an aurora A kinase inhibitor. (PubMed, Mol Cancer Ther) - "In vitro validation narrowed compounds of interest to raltitrexed, alisertib, GTX-007, LY315920, and PD0325901. Treatment with alisertib leads to decrease in H2AK119ub and shift in the immune tumor microenvironment. Alisertib efficacy in HGSC is dependent on functional CBX2 and cell target engagement confirms selectivity for CBX2, supporting that alisertib activity involves CBX2 inhibition."

Journal • Oncology • AURKA • CBX2

Resveratrol inhibits bladder cancer proliferation by targeting the AURKA/STAT3 axis: From computational analysis to experimental validation. (PubMed, PLoS One) - "Our findings suggest that Res may regulate BCa cell expression through the AURKA/STAT3 axis, providing a theoretical foundation for the structural optimization of Res and the development of multi-target drugs for clinical application."

IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • BCL2 • CCND1

Deciphering Mitotic and DNA Damage Pathways Driving Malignant Rhabdoid Tumour: Preclinical and Mechanistic Evaluation of Alisertib, Temozolomide, and Irinotecan Combination Therapy (LCC 2026) - "Conclusion Combination therapy with alisertib, TMZ and IRN produces potent synergistic efficacy in preclinical MRT PDX models through dual targeting of mitotic and DNA repair pathways. These findings provide compelling preclinical evidence to support the use of this combination in treating paediatric MRT."

Combination therapy • Preclinical • Oncology • Rhabdoid Tumor • Sarcoma • AURKA • SMARCB1

Bluish-gray hyperpigmentation associated with dual alisertib-osimertinib therapy (AAD 2026) - No abstract available

Results of a phase 1b study of osimertinib plus sapanisertib or alisertib for osimertinib-resistant, EGFR-mutant non–small cell lung cancer (NSCLC). (ASCO 2022) - P1 | "Osimertinib with alisertib or sapanisertib is well tolerated in osimertinib-resistant, EGFR mutant NSCLC. The sapanisertib combination, but not the alisertib combination, demonstrates antitumor activity suggesting that mTOR inhibition warrants further exploration in this population. Biomarker analysis is ongoing to identify the molecular determinants of response and resistance to sapasertib."

P1 data • Anemia • Dental Disorders • Diabetes • Hematological Disorders • Leukopenia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • AURKA • EGFR

Aurora Kinases as Potential Therapeutic Targets for Tumors with pRB and/or MYCN Dysregulation. (PubMed, Curr Cancer Drug Targets) - "In addition, we review the status of AURKA-specific inhibitors in clinical evaluation and their associated adverse effects. Finally, we cite the emerging therapeutic strategy of proteolysis targeting chimeras (PROTACs) as an innovative means to selectively degrade AURKs, offering a novel approach to targeted cancer therapy."

Journal • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • Targeted Protein Degradation • AURKA • AURKB • MYCN • RB1

Unhooking the Hook: Optimization of the Aurora A Targeting PROTAC JB170 to CCT400028, an In Vitro Degrader Chemical Probe. (PubMed, J Med Chem) - "In this study, we report the development of CCT400028, a second-generation alisertib-derived Aurora A PROTAC...Potent Aurora A degradation was shown in three pediatric tumor cell lines, as well as excellent selectivity and on-target mechanism of action. CCT400028 and a matched inactive control analogue fulfill the criteria for a degrader chemical probe for studying Aurora A degradation in vitro."

Journal • Preclinical • Oncology • Pediatrics • Targeted Protein Degradation • CRBN

Combinatory inhibition of Aurora Kinases and EZH2 leads to a synergistic antitumor effect in Triple Negative Breast Cancer (SABCS 2025) - P2 | "Aurora kinase inhibitors, such as alisertib (MLN8237), have demonstrated early signals of efficacy with a manageable safety profile for the treatment of patients with locally advanced or metastatic breast cancer (NCT02860000)...Furthermore, RNA-seq analysis of the TNBC cells treated with Aurora Kinases inhibitors (AKi) Barasertib (AZD1152) and/or EZH2 PROTAC degrader MS177 reveals that AKi inhibits the expression of a panel of genes, which EZH2 degrader also regulates...To summarize, we discovered Aurora Kinases have a less-studied, non-canonical oncogenic function, which acts in parallel with the canonical cell division activity to produce more aggressive tumor metastasis phenotypes seen in TNBC. This non-canonical function highly depends on EZH2-mediated cancer cell apoptosis, proliferation, invasion, and metastasis, which differs from the well-known cell division function of Aurora Kinases, regulating chromosomal alignment, segregation, and cytokinesis during..."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKB • EZH2

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) - P2 | " Three studies evaluating alisertib in patients with ER+/HER2- MBC have been completed, including a phase I study of alisertib + fulvestrant (Haddad 2018), a phase II alisertib monotherapy study (Melichar 2015), and a phase II study of alisertib ± fulvestrant (TBCRC 041; Haddad 2023). Alisertib has shown efficacy and safety across multiple clinical studies in patients with ER+/HER2- MBC and could provide a novel option for treating those who have progressed on endocrine therapy and a CDK 4/6i. These findings provide a strong rationale for further development of alisertib in this patient population. The ongoing phase II ALISCA-Breast1 study (NCT06369285) is investigating the optimal dose of alisertib in combination with standard endocrine therapies in this setting."

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

Stemness-targeted therapies to enhance the efficacy of AURKA inhibitors in endocrine resistant er+ breast cancer (SABCS 2025) - "CDK4/6 inhibitors(palbociclib, ribociclib, abemaciclib) have improved survival when combined with endocrine therapy.Nonetheless, resistance to CDK4/6 inhibitors eventually occurs...Despite such activity, alisertib resistance finally occurred.Therefore, we hypothesize that up-regulation of IL6R/STAT3 and PR stemness oncogenic pathwaysmay sustain the clonal expansion of CD44high/ALDHhigh CSCs after tumor progression on AURKAinhibitors.Experimental Design: We used variant MCF-7 breast cancer models that show resistance toendocrine therapy (letrozole and fulvestrant) and alisertib (MCF-7 LR/FR, MCF-7 LR/FR-AlisR) todefine in vitro and in vivo the efficacy of stemness-targeted therapies to enhance alisertib activity byimpairing the enrichment of hormone refractory CD44High/ALDHHigh CSCs...In Vivo Studies: 1x106breast cancer cells were injected into the mammary fat pad of NSG-female mice and treated withfulvestrant, alisertib and tocilizumab as monotherapy or in..."

Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CD44 • ER • IL6R • KLF4

Aurora Kinase A (AURKA) a new druggable target in ER+ Inflammatory Breast Cancer (SABCS 2025) - "Using ER- IBC cell lines we examined the protein expression of AURKA and tested Alisertib efficacy was tested using the crystal violet staining in IBC cell lines...We have characterized IBC models with high AURKA expression and demonstrated sensitivity to AURKA inhibition but senescence at higher doses which may provide a direction for targeting resistance or escape. Further studies in ER+ organoids are ongoing."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ARID1A • AURKA • HER-2 • IL6 • SMARCA4

Aurora A inhibitors enhance the efficacy of anti-tumor immunotherapy through the miR-644a/CTBP1/p53/NOXA axis (ESMO Asia 2025) - "MLN8237's effects on T-cell function and synergy with pembrolizumab (PD-1 inhibitor) were tested. Aurora A induces T-cell apoptosis via exosomal miR-644a/CTBP1/NOXA axis, reducing immunotherapy response. MLN8237 reverses this effect, suggesting synergy."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CTBP1 • MCL1 • MIR644A

Integrated Multi-Omics Profiling to Characterize Molecular Subtypes and Reveal Potential Therapeutic Strategies for Colorectal Cancer. (PubMed, MedComm (2020)) - "Moreover, it exhibited a higher stromal score, characterized by increased infiltration of fibroblasts, mesenchymal stem cells, and adipocytes, when compared with the S_II and S_III subtypes...Drug testing using cell lines and patient-derived three-dimensional (3D) bioprinted models revealed that S_I tumors were more responsive to Alisertib, suggesting subtype-specific therapeutic potential. Our study characterized the multi-omics landscape of CRC, offering critical insights into its molecular heterogeneity. These findings enhance our understanding of the molecular mechanisms underlying CRC and contribute to the development of personalized treatment strategies."

Journal • Colorectal Cancer • Oncology • Solid Tumor

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 (SNO 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 • Rhabdoid Tumor • Sarcoma • Solid Tumor • AURKA • SMARCA4 • SMARCB1

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 • Rhabdoid Tumor • Sarcoma • Solid Tumor • AURKA • SMARCA4 • SMARCB1

Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus (ASH 2023) - P1/2 | "Introduction: With the wider use of post-transplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis, there is interest in replacing tacrolimus (TAC) with sirolimus (SIR, mTOR inhibitor) to avoid calcineurin inhibitor toxicity, maintain excellent GVHD control, and potentially allow for a greater graft-versus-tumor effect...Patients undergoing myeloablative TBI-based alloHCT with PTCy/SIR plus mycophenolate mofetil (MMF), without VIC on a separate protocol, served as a control...Unlike alisertib, VIC-1911 is not myelosuppressive, providing rationale for this trial... A VIC-1911 dose of 75 mg BID from day +5 to day +45 effectively suppresses AURKA activity as determined by a low frequency of pH3ser10+ CD4+ T cells, ablating CD28 T cell costimulation when combined with sirolimus, resulting in no dose-limiting toxicities. VIC 75 mg BID will be studied further in an expanded phase I cohort to obtain estimates of efficacy in preventing both GVHD and..."

Combination therapy • P1 data • Acute Respiratory Distress Syndrome • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • AURKA • CD4

AURKA Kinase Controls Erythroblast Enucleation Via Regulation of Centrosome Localization and ECT2 Degradation (ASH 2023) - "Treatment of erythroblasts with MLN8237 (Aliseritib, AURKA selective inhibitor), AZD1152(Barasertib, AURKB selective inhibitor), or AT9283 (AURKA and AURKB inhibitor) dramatically blocked enucleation in a dose-dependent manner. The translocation of AURKA, which is originally restricted to centrosome relied on γ-tubulin interaction during nuclear polarization, was to directly degrade ECT2 at the anterior end of the protrusive nucleus for final nuclear expulsion. Our findings reveal a previously unrecognized localization and role of Aurora kinases in terminal erythroid differentiation and provide new mechanistic insights into erythroblast enucleation."

AURKA • AURKB • ECT2 • PLK4

Novel Causal Inference Method Estimates Treatment Effects of Contemporary Drugs in a Global Cohort of Patients with Relapsed and Refractory Mature T-Cell and NK-Cell Neoplasms (ASH 2023) - "Eligible patients received either a single agent (SA) such as an epigenetic modifier, small molecule inhibitor, brentuximab vedotin (BV) among others, or platinum-, gemcitabine-, ifosfamide-based cytotoxic chemotherapy (CC) in the second line setting...Patients with AITL treated with small molecule inhibitors (SMI) had greater OS compared to those treated with CC (p<.0005) and epigenetic modifiers (EM) (p=.001), with the most common SMIs including alisertib, duvelusib, cerdulatinib, and cyclosporine...As a causal analysis method, SI demonstrates the causal effect superiority of SA over CC in terms of survival outcomes for patients who responded differently to their 1st line treatment. Moreover, it achieves prediction accuracy comparable to, if not better than, Cox regressions, one of the most widely used methods in survival analysis."

Clinical • Hematological Malignancies • Lymphoma • Oncology

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

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