Synribo (omacetaxine mepesuccinate) / Teva, ArchiMed - LARVOL DELTA

Identification of repositioned inhibitors of pan-cancer proteasomal target as potential anti-proliferative candidates using a computational therapeutics approach. (PubMed, Biochem Biophys Res Commun) - "The compounds anisomycin, cephaeline, digitoxin, mitoxantrone, digoxin, digitoxigenin, homoharringtonine, NCI724448, midostaurin, withaferin A and NCI718581 were found to be effective UBE2C targeting candidates which could result in significant growth inhibition at low doses across multiple cell lines. Our results lay a strong groundwork for further preclinical exploration of the efficacy of these compounds against different cancers individually as also in combination with existing therapeutics for their future development as novel anticancer drugs."

Journal • Oncology • Targeted Protein Degradation • TP53 • UBE2C

Asciminib vs Dasatinib/Nilotinib as First-Line Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: A Propensity Score-Matched Analysis of Disease Progression and Safety Outcomes (SOHO 2026) - "The primary end point was disease progression between days 90 and 270, defined as escalation to ponatinib or omacetaxine, hematopoietic stem cell transplantation, or transformation to acute leukemia. The progression difference did not reach statistical significance, partly reflecting insufficient power to detect a moderate effect. Retrospective claims-level ascertainment of progression is imperfect, as some therapy switches may not represent true disease advancement. The cytopenia reduction with asciminib was substantial and statistically significant."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • BCR

Omacetaxine and venetoclax in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome with mutant RUNX1. (PubMed, Blood Neoplasia) - P1/2 | "Clinical responses were seen exclusively in patients with MDS, which suggests that dose optimization or combination with cytoreductive agents may be necessary for eliciting clinical activity in AML. This trial was registered at www.ClinicalTrials.gov as #NCT04874194."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • BCL2L1 • MCL1 • RUNX1

Venetoclax Combined with Hag Regimen in Newly Diagnosed ETP-ALL: A Prospective, Multicenter, Phase 2 Trial (ASH 2024) - "The V-HAG regimen included venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14; if the blast cells in the bone marrow (BM) were more than 5% on day 14, the patient continued to receive venetoclax 400 mg until day 28), homoharringtonine (1.4 mg/m², maximum 2 mg daily, intravenously from days 1-10), low-dose cytarabine (10 mg/m² subcutaneously every 12 hours on days 1-14), and G-CSF (200 µg/m² daily on days 1-14 if the WBC <10*109/L). Conclusions : Venetoclax Combined with HAG regimen achieved an 100% CRc rate in newly diagnosed ETP-ALL. This therapy is a promising and well-tolerated regimen in newly diagnosed ETP-ALL patients."

Clinical • P2 data • Acute Lymphocytic Leukemia • Anemia • Basal Cell Carcinoma • Bone Marrow Transplantation • Chronic Obstructive Pulmonary Disease • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Melanoma • Neutropenia • Non-melanoma Skin Cancer • Oncology • Respiratory Diseases • Solid Tumor • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thrombocytopenia • Thyroid Gland Carcinoma • Tuberculosis

Olverembatinib (HQP1351) Demonstrates Efficacy Vs. Best Available Therapy (BAT) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant Chronic Myeloid Leukemia Chronic-Phase (CML-CP) in a Registrational Randomized Phase 2 Study (ASH 2023) - P2 | "Introduction This was a multicenter, randomized, registrational phase 2 study to assess the efficacy and safety of olverembatinib compared with BAT in pts with CML-CP who were resistant and/or intolerant to 3 TKIs (imatinib [I], dasatinib [D], nilotinib [N]) in China...Pts were randomized 2:1 to investigational olverembatinib (40 mg QOD) or the BAT arm, which could be one of the following per investigator choice: TKIs (I, D, or N), interferon (IFN), hydroxyurea (HU), and homoharringtonine (HHT)...Olverembatinib was observed to be better tolerated and more effective than BAT in treating these pts. Internal study (CT.gov) numbers: HQP1351CC203 (NCT04126681)."

Clinical • P2 data • Anemia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Leukemia • Leukopenia • Myocardial Infarction • Neutropenia • Oncology • Thrombocytopenia • ABL1

Drug repurposing strategies targeting core pathways in glioblastoma to address heterogeneity (EANO 2026) - "Standard treatment includes surgical resection, radiation, and temozolomide chemotherapy; however, 80-90% of patients experience relapse...Of these, three were prioritized for further investigation based on their targeting of essential cellular pathways, in particular we selected: Homoharringtonine (a protein synthesis inhibitor), Ixazomib citrate (a proteasome inhibitor), and Panobinostat (a histone deacetylase inhibitor)... These findings demonstrate that targeting core cellular pathways in TICs is a feasible and clinically actionable strategy to counteract GBM heterogeneity and therapeutic resistance. This approach offers the potential for broadly effective treatments. Ongoing studies aim to expand the compound panel, investigate resistance mechanisms using single-cell transcriptomic and epigenomic profiling, and develop optimized combination therapies to improve outcomes for patients with GBM."

Heterogeneity • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

MRD-positive AML Clinical Study (clinicaltrials.gov) - P=N/A | N=537 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | N=120 ➔ 537 | Trial completion date: Apr 2028 ➔ Oct 2028 | Trial primary completion date: May 2026 ➔ May 2028

Enrollment change • Minimal residual disease • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • DEK • FLT3 • NPM1 • NUP214 • RUNX1 • RUNX1T1

Hypoplastic acute myeloid leukemia with aberrant lymphoid antigen expression and EWSR1::FEV fusion: A rare case report and literature review. (PubMed, Ther Adv Hematol) - "The patient achieved morphological complete remission after one cycle, accompanied by a marked reduction in EWSR1::FEV transcript levels, and remained in morphological remission during approximately 6 months of follow-up after subsequent homoharringtonine combined with venetoclax plus azacitidine (HVA) consolidation. Together with previously reported cases, this case further supports the notion that EWSR1::FEV-positive acute leukemia may represent a distinct molecular subset characterized by lineage ambiguity, fusion-driven biology, and potentially unique therapeutic vulnerabilities. This case also suggests potential activity of venetoclax-based therapy in EWSR1::FEV-positive leukemia and warrants further investigation in additional cases."

Journal • Acute Myelogenous Leukemia • Ewing Sarcoma • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor • EWSR1 • FLI1 • NRAS • PTPN11

HLA-AML: Homoharringtonine, Lisaftoclax, and Azacitidine for AML After Venetoclax-Based Therapy Failure (clinicaltrials.gov) - P2 | N=73 | Enrolling by invitation | Sponsor: Guangdong Second Provincial General Hospital

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

Successful induction of remission with azacitidine, venetoclax, and dasatinib followed by allogeneic hematopoietic stem cell transplantation in a patient with Philadelphia chromosome-positive mixed phenotype acute leukemia (B/myeloid): a case report. (PubMed, Front Med (Lausanne)) - "The patient received one cycle of induction therapy with azacitidine, venetoclax, and dasatinib, augmented with Vincristine, prednisone, and homoharringtonine. At the most recent follow-up, BCR::ABL1 was undetectable. An induction regimen based on azacitidine, venetoclax, and dasatinib may represent a safe and effective therapeutic strategy for adult patients with Ph+, bilineal MPAL, particularly when augmented with agents targeting distinct lineage components."

Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Transplantation • ABL1 • ASXL1

Epithelial tumor suppressor deletion promotes neuroendocrine differentiation in bladder cancer and reveals homoharringtonine as a candidate vulnerability. (PubMed, Oncogene) - "HHT suppressed neuroendocrine marker expression, induced apoptosis, and attenuated IL6-JAK-STAT3 signaling. Together, these findings describe complementary epithelial-derived NEBC models and support further investigation of HHT as a candidate therapeutic vulnerability."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Sarcoma • Solid Tumor • IL6 • RB1 • TP53

A self-initiating battery-like hydrogel for autonomous pH normalization and immune activation in postoperative tumor therapy. (PubMed, Biomaterials) - "Meanwhile, embedded homoharringtonine-loaded nanoparticles were encapsulated in the hydrogel to promote M2 to M1 macrophages polarization. Fortunately, this system eliminates residual tumor cells and remodels the immunosuppressive microenvironment, resulting in ∼95% suppression of tumor recurrence, while preventing metastasis and establishing durable immune memory. With biocompatible components and flexible architecture suitable for irregular tumor beds, this battery-like hydrogel serves as a promising immunotherapeutic platform for postoperative tumor management."

Journal • Metabolic Disorders • Oncology

Novel Agents with Efficacy Against Cellular Models of Familial Platelet Disorder with Myeloid Malignancy (FPD-MM) Associated with Germline Mutant RUNX1 (ASH 2023) - "LINCS1000-CMap analysis, conducted with the RNA-Seq signature induced by lethal RUNX1 knockdown in AML cells with mutant (mt) RUNX1, was reported by us to reveal homoharringtonine (HHT or omacetaxine) and the anthelmintic fenbendazole (analog of mebendazole) as the top expression mimickers (EMs). These preclinical findings highlight the molecular features associated with progression of RUNX1-FPD to FPD-MM, including the newly established GMR-AML1 cell line. They also demonstrate that HHT or MB are effective against cellular models of FPD-MM versus RUNX1-FPD."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • BCL2 • BCOR • CCND2 • CD123 • CD33 • CD34 • CDK6 • IL3RA • KIT • KRAS • MCL1 • MECOM • MYC • PHF6 • PTPN11 • RRM2 • RUNX1 • TET2 • WT1

Novel agents with efficacy against germline mutant RUNX1 familial platelet disorder with myeloid malignancy (FPD-MM) (AACR 2024) - "LINCS1000-CMap analysis, of the RUNX1 knockdown RNA-Seq signature revealed homoharringtonine (HHT or omacetaxine) and the anthelmintic fenbendazole (analog of mebendazole (MB)) as the top expression mimickers. Finally, in the GMR-AML1 cell xenograft, treatment with omacetaxine or MB significantly reduced AML burden and improved overall survival of NSG mice. These preclinical findings highlight the molecular features associated with progression of RUNX1-FPD to FPD-MM and highlight HHT or MB as effective against cellular models of FPD-MM."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology • BCL2 • CD123 • CD33 • CDK6 • IL3RA • KIT • MCL1 • MECOM • MYC • RUNX1

Heat shock protein family D member 1 (HSPD1) modulates ribosome-related pathways and protein synthesis in lung adenocarcinoma. (PubMed, Mol Cell Biochem) - "Moreover, HSPD1 knockdown sensitized cells to homoharringtonine, a chemotherapeutic drug targeting ribosomal activity. These effects on cell proliferation, ribosomal protein levels, and drug sensitivity were validated in an independent LUAD cell line, H1975. Collectively, these findings indicate that HSPD1 acts as an oncogenic driver in LUAD by modulating ribosome-related pathways and protein synthesis."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HSPD1 • RPS3

HADCEBPA2023: Intermediate-dose HAD Regimen for CEBPA Double-mutated AML (clinicaltrials.gov) - P=N/A | N=148 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Trial completion date: Sep 2028 ➔ Sep 2029 | Trial primary completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CEBPA

RR-AML-2023: Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia (clinicaltrials.gov) - P=N/A | N=458 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | N=120 ➔ 458 | Trial completion date: Jun 2026 ➔ Jun 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2028

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Case Report: Early T-cell precursor acute lymphoblastic leukemia with aberrant CD19 expression and an NPM1 mutation. (PubMed, Front Oncol) - "After management of severe sepsis, the patient received three cycles of VHAG (venetoclax, homoharringtonine, cytarabine, and granulocyte colony-stimulating factor)-based chemotherapy followed by haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). He remained in sustained complete remission at the 7-month follow-up after allo-HSCT. To our knowledge, this case represents the first reported ETP-ALL with an NPM1 frameshift mutation (p.W288Cfs*12, Type A), which also exhibited aberrant CD19 expression, highlighting the diagnostic challenges posed by unusual immunophenotypic and genomic profiles."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Septic Shock • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • CD19 • CD1a • CD22 • CD33 • CD34 • CD5 • CD7 • CD79A • CD8 • FLT3 • MME • MPO • NPM1

Establishment of a Doxorubicin-Resistant Acute Myeloid Leukemia Cell Line and Study on Its Drug Resistance Mechanisms (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi) - "Low-dose, concentration-gradient intermittent induction method can successfully establish a DOX-resistant AML cell line, THP1-Rdox. The drug resistance of this cell line is likely attributed to enhanced drug efflux mediated by the elevated expression of P-gp and LRP, as well as cell cycle dysregulation resulting from the upregulation of Cyclin D1 protein."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABCB1 • CCNA2 • CCNB1 • CCND1 • CLEC1B • DTX3 • GBP5 • GLI2 • MAGEB2

Single-cell and longitudinal transcriptomics-guided engineering of FZD1-targeting precision nanotherapy against osteosarcoma cancer stem cells. (PubMed, Bioact Mater) - "To enhance efficacy while reducing systemic toxicity, an FZD1-targeted, pH/glutathione dual-responsive nanoplatform was engineered to achieve precise drug delivery to OCSC-derived tumors via high-affinity binding of UM206 peptide to FZD1, concurrently enabling tumor microenvironment-triggered homoharringtonine release in acidic, glutathione-rich niches. This integrated approach characterizes OCSC-associated transcriptional regulation and supports further development of OCSC-targeted precision nanotherapies for osteosarcoma."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • TCF7

Homoharringtonine in combination with Tanshinone IIA suppresses the progression of lymphoma cells by downregulating the Akt/MMP signaling pathway. (PubMed, Cytotechnology) - "HHT and Tan IIA combined therapy synergistically suppressed lymphoma progression by downregulating the Akt/MMP signaling pathway, suggesting their use in treating lymphomas. Clinical trial number: Not applicable."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • MMP2 • MMP9 • VEGFC

Cephalotaxinone enzymes reveal a whole plant model for homoharringtonine biosynthesis. (PubMed, Nat Chem Biol) - "We identify seven pathway intermediates and six enzymes-including cytochrome P450s, an atypical short-chain dehydrogenase and a 2-oxoglutarate-dependent dioxygenase-that enable carbon excision and CET/HHT pentacyclic backbone formation to produce cephalotaxinone, the likely direct precursor of CET. This study establishes a metabolic route to the HHT core and suggests a whole-plant coordination model, in which cephalotaxinone is produced in root tips and distributed for elaboration into HHT."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

A Novel Magnetically Targeted Intramedullary (MagIC-TI) Xenograft Model for Precise Leukemia Modeling and Drug Resistance Evaluation in the Bone Marrow Niche. (PubMed, J Immunol Res) - "Magnetically labeled doxorubicin (DOX)-resistant HL60 cells (Mag-Re) were injected into the femurs of NSG (nonobese diabetic [NOD] Cg-PrkdcscidIL2rgtm1Wjl/SzJ) mice using a patented microinjection syringe under localized magnetic guidance...The MagIC-TI model discriminated drug responses, showing effective tumor burden reduction with homoharringtonine (HHT) and unequivocal DOX resistance, a distinction that was obscured in heterogeneous IV models...The MagIC-TI model enables BM-targeted, rapid, and efficient leukemic engraftment and allows discrimination of drug sensitivity and resistance. This model provides a robust and reproducible platform for modeling the leukemia BM niche and for preclinical evaluation of niche-directed therapies."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Obesity • Oncology • PRKDC

Homoharringtonine Impedes Migration and Invasion by Inhibiting EphB4/SRI/EMT Signaling and Enhances the Antimetastatic Abilities of Erlotinib in Pancreatic Cancer. (PubMed, Curr Cancer Drug Targets) - "HHT has been identified as an impediment to cell invasion and metastasis in PC via the EphB4/SRI/EMT axis. Additionally, HHT enhances the efficacy of ERT in inhibiting the migration of PC cells."

Journal • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Solid Tumor • CDH1 • CDH2 • EPHB4 • SRI

Investigating translation inhibition for the treatment of transcription inhibitor resistant Group 3 medulloblastoma (ISPNO 2026) - "By demonstrating that this resistance can be reversed through combined transcriptional and translational inhibition, our work highlights omacetaxine as a promising therapeutic agent for relapsed disease. Ongoing work will further dissect the specific post-translational modifications contributing to MYC persistence and validate these combination strategies in orthotopic xenograft models, with the ultimate goal of informing novel clinical trials for children with high-risk MBL."

Brain Cancer • Medulloblastoma • Solid Tumor • MCL1 • PODXL