Our research revealed comprehensive metabolic alterations in gastric cancer, including upregulated lactate metabolism that promotes tumorigenesis via the lactate shuttle. Niclosamide targets the m6A methylation regulatory protein YTHDF2, which influences genes related to metabolism, indicating its potential as a prospective treatment for GC.

Tyrosine kinase inhibitors (TKIs), such as sunitinib and sorafenib, are standard treatments for renal cell carcinoma (RCC). RNA sequencing (RNA-seq) and bioinformatic analyses showed that niclosamide modulated critical pathways, including BRIP1- and FANCA-mediated DNA repair and E2F2-regulated cell cycle progression. These findings provide proof-of-concept that niclosamide enhances TKI efficacy through modulation of DNA repair and cell cycle pathways, supporting the rationale for DNA damage response (DDR)-targeted combination strategies in RCC.

Given the reduced ATP-generating capacity of SDHB -KO cells, we hypothesized they would be uniquely sensitive to futile cycle induction with mitochondrial ionophores (2,4-Dinitrophenol (2-DNP), BAM15, Niclosamide, Nitazoxanide). Thus, the accumulation of succinate in SDH-deficient tumors inhibits KDM4 activity, impairs DNA repair and yields enhanced susceptibility to Ym155-induced reactive oxygen species (ROS) generation. The identified intrinsic susceptibilities of SDHB -deficient cancers has the potential to be therapeutically leveraged.

High-risk tumors owned shorter overall survival time, but were suitable for treatment with docetaxel and several small-molecule agents (MK-0752, BRD-K33199242, IC-87114, fumonisin B1, ilomastat, GW-788388, afobazole, and batimastat). Experimentally, inhibition of FAM129B effectively attenuated proliferative and aggressive phenotypes of TNBC cells. Collectively, our findings proposed the exosome-based gene signature for accurate estimation of clinical outcomes and assisting in individually tailoring therapies in TNBC as well as discovered FAM129B as a potential therapeutic target.

P1, N=44, Active, not recruiting, Immunome, Inc. | Recruiting --> Active, not recruiting

Emerging breakthroughs in targeted therapies warrant attention, including antisense oligonucleotides targeting MYB-NFIB fusion genes, clinical trial data of NOTCH inhibitors (e.g., AL101), and PARP inhibitor-based combinatorial regimens leveraging DNA damage repair mechanisms. By integrating fundamental research and clinical translational evidence, this review provides a theoretical framework for optimizing LGACC diagnosis and treatment paradigms.

Herein, we developed a mito-specific "Trojan Horse" nanoplatform (2-pN@LNPs) coloaded with Niclosamide (Nic) and 2-deoxy-d-glucose (2-DG) to attack key metabolism pathways and synergistically ignite pyroptosis for restoring antitumor immunity. Moreover, the synergistic treatment regimen can promote cytotoxic and helper T cells (CD8+/CD4+ T cells) recruitment and M1-type macrophage polarization, facilitating the establishment of a boost in immunological memory to prevent recurrence and metastasis. Overall, this work provides a robust strategy targeting metabolism through mitochondrial uncoupling and glycolysis inhibition, which can effectively improve the antitumor effect, inhibit lung metastasis, and help modulate antitumor immunity.

P1, N=6, Completed, Immunome, Inc. | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Mar 2025 | Trial primary completion date: Jul 2025 --> Mar 2025

P1, N=32, Completed, Immunome, Inc. | Active, not recruiting --> Completed

Therapeutic options are minimal, with nitazoxanide (NTZ) being the only drug available, despite its constrained effectiveness...Mice were immunosuppressed using dexamethasone, infected with C. parvum oocysts, and administered NTZ or NICLO...These findings highlight NICLO's dual therapeutic potential, which effectively targets C. parvum infection and mitigates its tumorigenic effects by disrupting key signaling pathways involved in ileocecal cancer progression. This study provides novel insights into NICLO's chemotherapeutic efficacy in managing cryptosporidiosis and its associated oncogenic potential.

Notably, lycorine enhanced the antitumor activity of osimertinib against its resistant cells both in vitro and in vivo. Overall, our data reveal that lycorine inhibits the proliferation and metastasis of osimertinib-resistant NSCLC cells via Notch3/Hes1 pathway.

In addition, the LEF1 inhibitor niclosamide increased ovarian cancer sensitivity to Cisplatin and PARPi in patient-derived organoids and Niraparib-resistant cell lines. These findings indicate that LEF1 is a potential therapeutic target for overcoming resistance to chemotherapy based on platinum and PARPi in EOC.