P1/2, N=24, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; The study terminated early because the company was longer providing the investigational product.

We then evaluated the response of these mutant cells to a panel of compounds targeting protein synthesis at various levels-including an MNK1 inhibitor, metformin, silvestrol, homoharringtonine, anisomycin, resveratrol, and hygromycin B-as well as cytarabine, a chemotherapeutic agent commonly used in T-ALL treatment. Our results showed that the RPL5-I60V mutation confers increased sensitivity to most of these compounds, with the exception of hygromycin B. This study advances our understanding of how oncoribosomes contribute to cancer pathogenesis and highlights the therapeutic potential of directly or indirectly targeting altered ribosomes, offering insights for the development of personalized treatment strategies.

P1/2, N=62, Not yet recruiting, The First Affiliated Hospital, Zhejiang University College of Medicine; The First Affiliated Hospital of Zhejiang University Medical College

P1/2, N=28, Active, not recruiting, University of Colorado, Denver | Trial primary completion date: Aug 2025 --> Aug 2026

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.

P1/2, N=62, Not yet recruiting, First Affiliated Hospital of Zhejiang University

Methyl-angolensate, byssochlamic-acid, homoharringtonine, piperacillin and cephaeline were potentially targeted therapeutic compounds for hub genes based on molecular docking. Our study firstly provides new insight into the genetic crosstalk between metastatic melanoma and vitiligo that may facilitate the development of personalized treatments.

P2/3, N=610, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

We established the stromal-AML co-culture system (HS-5 cells with U937, HL-60, and primary AML cells) and the humanized mouse AML model to systematically evaluate eIF4E's role in modulating homoharringtonine (HHT) and arsenic trioxide (ATO) cytotoxicity within the leukemic microenvironment. Genetic perturbation studies demonstrated that eIF4E knockdown sensitized AML cells to HHT/ATO, whereas its overexpression conferred therapeutic resistance. eIF4E may play an essential role in mediating the cytotoxic effects of HHT and ATO, representing a novel therapeutic target in AML.

Moreover, elevated DDX41 levels increase liver cancer cell sensitivity to protein synthesis inhibitors; treatment with homoharringtonine (HHT), an approved drug, significantly inhibits tumor growth in DDX41-overexpressing liver cancer models. Taken together, the results of this study highlight that DDX41 acts as an oncogene in liver cancer and suggest that protein synthesis inhibition may be a promising therapy for liver cancers with high DDX41 expression.

FLT3-ITD AML cells represent a responsive subgroup to HHT treatment in vitro and in vivo. The combination of HHT and quizartinib demonstrates optimal efficacy and selectivity against FLT3-ITD AML cells in xenografts, with no observed toxicity.

For example, homoharringtonine (HT), a She-derived alkaloid, targets Smad3/TGF-β pathways in non-small cell lung cancer and synergizes with chemotherapy in leukemia treatment, as evidenced by preliminary clinical trials...Future research should integrate multi-omics and bioengineering approaches to standardize She Medicine and bridge its traditional use with modern therapies such as immune checkpoint inhibitors. Overall, She medicinal herbs hold great promise for cancer treatment and warrant further exploration to unlock their full potential in modern medicine.