lestaurtinib (CEP-701) / Teva, Kyowa Kirin - LARVOL DELTA

ESAM is functionally involved in the activity of cancer stem-like cells in human acute myeloid leukemia (ASH 2025) - "However, upon treatment with FLT3 inhibitors (CEP701 and quizartinib), ESAM-expressingcells retained heigh drug sensitivity. ESAM enhances biological activity of AML LSCs, likely through modulation ofsignaling pathways and interactions with junctional and membrane-associated proteins. These findingsidentify ESAM as a key regulator of LSC behavior and a potential therapeutic target in AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Targeted Protein Degradation • FLT3 • TJP1 • ZKSCAN1 • ZNF23

Lestaurtinib's antineoplastic activity converges on JAK/STAT signaling to inhibit treatment naïve and therapy resistant forms ovarian cancer. (PubMed, NPJ Precis Oncol) - "Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. Concordantly, combinatorial treatment with ruxolitinib and a JNK or ERK inhibitor resulted in synergistic antineoplastic effects at dose levels where the single agents were ineffective. Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • STAT3

Lestaurtinib’s antineoplastic activity converges on JAK/STAT signaling to inhibit treatment naïve and therapy resistant forms ovarian cancer (Nature) - "RNA-sequencing revealed that lestaurtinib potently suppressed JAK/STAT signaling and lestaurtinib efficacy was shown to be directly related to JAK/STAT pathway activity in cell lines and PDX models. Most ovarian cancer cells exhibited constitutive JAK/STAT pathway activation and genetic loss of STAT1 and STAT3 resulted in growth inhibition. Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested. This divergent behavior was reflected in the ability of lestaurtinib to block both Y701/705 and S727 phosphorylation of STAT1 and STAT3, whereas ruxolitinib failed to block S727. Consistent with these findings, lestaurtinib additionally inhibited the serine/threonine kinases, JNK and ERK, leading to more complete suppression of STAT phosphorylation."

Preclinical • Ovarian Cancer

The Androgen Receptor-Serum Response Factor Network As a Pharmacological Target in Castration Resistant Prostate Cancer. (EACR 2025) - "Small molecule inhibitors include SRF inhibitors (CCG1423, Lestaurtinib), AR/ARv7 inhibitors (Enzalutamide, EPI7170) and common co-factor inhibitors (VER-15508, JG-98, Ganetespib, Ipatasertib, Alpelisib). To conclude, our results indicate that targeting the AR-SRF intracellular network holds promise as a treatment option for patients with CRPC. Combination treatments were shown to bypass resistance mechanisms in our CRPC cell line models and are synergistic at lower concentrations. Furthermore, by studying the proteomic and phosphor-proteomic landscape before and after treatments, we can further understand disease and resistance mechanisms in PCa as well as find potential novel targets which can be used for the disease."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CDC37 • HSP90AA1

Targeting CITK in high-grade brain tumors: a comparison of polypharmacological and specific inhibitors (EACR 2025) - "Compared to a polypharmacological inhibitor, more specific CITK catalytic inhibitors may recapitulate the effects of protein knockdown, but to a lesser extent and in a cell line-dependent manner. Given that the data on different cell lines show a varied response to CITK inhibition, we have begun to explore the genes and pathways that make a cell line sensitive to CITK, with the aim of predicting in the future which lines would be more responsive to treatment."

Brain Cancer • Endocrine Disorders • Glioblastoma • Medulloblastoma • Oncology • Solid Tumor

Calcium-dependent adhesion protein CDH18, a potential biomarker for prognosis in uterine corpus endometrial carcinoma. (PubMed, Front Mol Biosci) - "In the group with high CDH18 expression, the IC50 values for (5Z)-7-Oxozeaenol, AG-014699, CEP-701, Mitomycin C, PD-0325901, PD-0332991, PHA-665752, SL 0101-1, and SN-38 were notably elevated. CDH18 is a novel promising biomarker in UCEC, uniquely associating tumor progression, immune modulation, and chemotherapy resistance, offering enhanced prognostic accuracy and guiding individualized therapeutic strategies for improved patient outcomes."

Biomarker • Journal • Tumor mutational burden • Endometrial Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Uterine Cancer • CD8 • CDH18 • MUC16 • TMB

Protocol to infer off-target effects of drugs on cellular signaling using interactome-based deep learning. (PubMed, STAR Protoc) - "As a case study, we analyze the off-target effects of lestaurtinib on FOXM1 in the A375 cell line. For complete details on the use and execution of this protocol, please refer to Meimetis et al.1."

Journal • FOXM1

This Month in JAAD International: March 2025: Weight gain and Janus kinase inhibitors. (PubMed, J Am Acad Dermatol) - No abstract available

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Psoriasis

Efficacy of FLT3 Inhibitors in Acute Myeloid Leukemia (AML): A Network Meta-Analysis of Randomized Controlled Trials (SOHO 2024) - "Nonsignificant combinations, in decreasing order of effect, were midostaurin + CT + HSCT (HR, 0.8114 [0.5192-1.2681]), sorafenib + CT (HR, 0.8182 [0.6239-1.0730]), gilteritinib + HSCT (HR, 0.8307 [0.5170-1.3348]), sorafenib + HSCT (HR, 0.8834 [0.5367-1.4539]), and lestaurtinib + CT (HR, 0.9056 [0.7642-1.0731]). Our analysis shows that quizartinib + CT + HSCT and gilteritinib + CT significantly reduce mortality risk compared with chemotherapy ± HSCT. Incremental effects analysis highlights significant benefits for quizartinib, midostaurin, gilteritinib, and sorafenib, indicating their efficacy in managing FLT3-mutated AML."

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Type II mode of JAK2 inhibition and destabilization are potential therapeutic approaches against the ruxolitinib resistance driven myeloproliferative neoplasms. (PubMed, Front Oncol) - "Our study identifies JAK1 and JAK2 resistance variants against the type I JAK2 inhibitors ruxolitinib, fedratinib, and lestaurtinib. The sensitivity of these resistant variants towards the type II JAK2 inhibitor CHZ-868 indicates that this mode of type II JAK2 inhibition is a potential therapeutic approach against ruxolitinib refractory leukemia. This also proposes the development of potent and specific type II JAK2 inhibitors using ruxolitinib-resistance variants as a prototype."

Journal • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • CDC37 • JAK1 • STAT5 • STAT5AWqe

AALL0631: Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=218 | Completed | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

A cellular senescence-related signature for predicting prognosis, immunotherapy response, and candidate drugs in patients treated with transarterial chemoembolization (TACE). (PubMed, Discov Oncol) - "This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CDK1 • CHEK1 • FOXM1 • SERPINE1

Lestaurtinib's antineoplastic activity converges on JAK/STAT signaling to inhibit advanced forms of therapy resistant ovarian cancer. (PubMed, bioRxiv) - "Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested...Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer. Lestaurtinib is a novel inhibitor of ovarian cancer, including chemotherapy- and PARPi-resistant models, that acts through robust inhibition of the JAK/STAT pathway and synergizes with standard-of-care agents at clinically relevant concentrations."

Journal • Metastases • Colorectal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • STAT3

[PREPRINT] Lestaurtinib’s antineoplastic activity converges on JAK/STAT signaling to inhibit advanced forms of therapy resistant ovarian cancer (bioRxiv) - "RNA-sequencing revealed that lestaurtinib potently suppressed JAK/STAT signaling and lestaurtinib efficacy was shown to be directly related to JAK/STAT pathway activity in cell lines and PDX models. Most ovarian cancer cells exhibited constitutive JAK/STAT pathway activation and genetic loss of STAT1 and STAT3 resulted in growth inhibition. Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested. This divergent behavior was reflected in the ability of lestaurtinib to block both Y701/705 and S727 phosphorylation of STAT1 and STAT3, whereas ruxolitinib failed to block S727. Consistent with these findings, lestaurtinib additionally inhibited JNK and ERK activity, leading to more complete suppression of STAT phosphorylation."

Preclinical • Preprint • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials. (PubMed, Front Pharmacol) - " We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023...The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication."

Monotherapy • Review • Acute Myelogenous Leukemia • Dermatology • Febrile Neutropenia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • FLT3

FLT3-ITD MICROCLONES ARE DETECTED AT RELAPSE IN PATIENTS WITH FLT3-ITD AML AFTER INTENSIVE CHEMOTHERAPY (EHA 2024) - "58 patients(43%) received induction with IC + TKI (15 lestaurtinib, 22 midostaurin, 20 sorafenib, 1 quizartinib) and 78patients (57%) received induction with IC only. In patients with FLT3-ITD AML relapsing after IC, there is a trend to more frequent loss of FLT3-ITD clones atrelapse using CE in patients receiving prior TKIs. Microclones (CE negative) were detected in 19% at clinicalrelapse, with a trend for higher frequency among patients with prior TKI exposure. Although this study did notshow evidence for inferior prognosis related to the presence of microclones at relapse, a larger cohort will beneeded to determine the natural history of these microclones and potential role for FLT3 inhibitors as part ofsalvage therapy."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma. (PubMed, Expert Rev Mol Diagn) - "The prediction of IC50 based on bioinformatics method indicated DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. In accordance with the prediction, cytotoxicity assay in DLBCL cell lines suggested the higher sensitivity to doxorubicin and gemcitabine in the high-risk group and the higher sensitivity to dasatinib in the low-risk group in DLBCL. The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCND1 • HIF1A • IGF1 • PDK4 • PTEN

Identifying the predictive role and the related drugs of oxidative stress genes in the hepatocellular carcinoma. (PubMed, Cancer Rep (Hoboken)) - "Our findings indicate that OS related-genes have a favorable prognostic value for HCC, which sheds new light on the relationship between oxidative stress and HCC, and suggests potential therapeutic strategies for HCC patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Inference of drug off-target effects on cellular signaling using interactome-based deep learning. (PubMed, iScience) - "As a case study, we analyze the effects of the drug Lestaurtinib on downstream signaling. Alongside its intended target, FLT3, the model predicts an inhibition of CDK2 that enhances the downregulation of the cell cycle-critical transcription factor FOXM1. Our approach can therefore enhance our understanding of drug signaling for therapeutic design."

Journal • FLT3 • FOXM1

Targeting the Androgen Receptor and Serum Response Factor Molecular Network in a Model of Castrate Resistant Prostate Cancer (EACR-AACR 2024) - "Introduction Advanced prostate cancer (PCa) is often treated with surgery, radiation and therapies that target the androgen receptor (AR) pathway, such as enzalutamide (enza)...Inhibitors that target the SRF pathway, such as CCG1423, CCG257081 and lestaurtinib (lesta) were combined with enza to determine cell viability and possible synergy...Inhibition of HSP70, HSP90 and AKT using JG-98, Ganetespib and Ipatasertib respectively, in the LNCaP Parental and Abl cells show significantly reduced cell viability with IC 50 concentrations in the nanomolar range compared to enza, which is effective at µM concentrations. Conclusion Targeting the SRF pathway holds promise in the treatment of CRPC. Furthermore, investigation of the AR/SRF axis reveals a pipeline of targets for future therapeutic intervention."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDC37 • HSP90AA1

Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS. (PubMed, ACS Omega) - "Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • NOS3

Novel janus-kinase (JAK) inhibitors in myelofibrosis. (PubMed, Expert Opin Investig Drugs) - "This review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate...In patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS)...The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs."

Journal • Review • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

The promising impact of Bemcentinib and Repotrectinib on sleep impairment in Alzheimer's disease. (PubMed, J Biomol Struct Dyn) - "Multiple compounds from three biomolecule libraries (719 compounds; ChemDiv:366 - ChEMBL:180 - PubChem:173) were evaluated for potential binding affinity and safety using AutoDock Vina and pkCSM, respectively, resulting in the selection of four candidate compounds (Lestaurtinib, Repotrectinib, Bemcentinib, and Zotiraciclib). We report Bemcentinib and Repotrectinib, formerly prescribed for cancer, as potential inhibitors of the CK1 δ. Besides their high binding affinity compared to ATP, they can inhibit all ATP-binding sites and alter the tau binding stability.Communicated by Ramaswamy H. Sarma."

Journal • Alzheimer's Disease • CNS Disorders • Insomnia • Oncology • Sleep Disorder

Cytosolic DNA accumulation promotes breast cancer immunogenicity via a STING-independent pathway. (PubMed, J Immunother Cancer) - "This work demonstrated that cytosolic ssDNA accumulation promotes breast cancer immunogenicity and may be a novel therapeutic strategy to improve the efficacy of ICB with minimal toxicities."

Journal • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • DDX3X • STING

Cytosolic DNA accumulation promotes breast cancer immunogenicity via a STING-independent pathway (J Immunother Cancer) - "We found the tumorous cytosolic ssDNA is associated with tumor-infiltrating lymphocyte in patients with triple negative breast cancer. TREX1 deficiency triggered a STING-independent innate immune response via DDX3X. Cytosolic ssDNA accumulation in tumors due to TREX1 deletion is sufficient to drastically improve the efficacy of ICB. We further identified a cytosolic ssDNA inducer CEP-701, which sensitized breast tumors to ICB without the toxicities associated with inhibiting DNA damage response."

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