Vumon (teniposide)

P2, N=200, Not yet recruiting, Peking University Shenzhen Hospital

P4, N=30, Not yet recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

We have uncovered a novel role of Teniposide, which when used at a very low concentration, mitigates mesenchymal-like invasive phenotype. Overall, its ability to target EMT and rRNA biogenesis makes Teniposide a viable candidate to be repurposed as a therapeutic option to restrict breast cancer metastases.

The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM.

Our findings emphasizes the role of disulfidptosis in regulating tumor development, therapeutic response, and patient survival in CRC patients. For the clinical treatment of CRC, these important LncRNAs could serve as viable therapeutic targets.

Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.

Metabolic alteration mediated by hypoxia and TP53 mutation is associated with TME modulation and tumor progression across cancer types. In this study, we analyzed the role of metabolic alteration in cancer and propose a predictive model for cancer prognosis and immunotherapy responsiveness. We also explored a potential therapeutic drug, teniposide.

This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses.

We investigated the differences in prognosis, TIM, and drug treatment response between LCC and RCC patients, which may contribute to accurate colon cancer prognosis and treatment of colon cancer.

These results correlated with increased response to the proapoptotic drugs talazoparib, teniposide and the IRAK4 inhibitor emavusertib(p=0.043/0.037/0.027). The combination of emavusertib and alpelisib had the greatest synergy in MUT and WT HER2 BC cells.ConclusionThe 9177 mutation, present in 15% of HER2+ patients, impacts expression of HER2 amplicon genes and altered expression of apoptosis regulating proteins. The dual inhibition of IRAK and PI3K pathways has synergistic anti-proliferative effects and represents a potential novel treatment for HER2 BC patients.

No abstract available

We generated A2780 and OVCAR4 ovarian cancer cells resistant to JMS-053, and the resulting cells were not crossresistant to paclitaxel, cisplatin, or teniposide. Significance Statement We demonstrate that chemical inhibition of PTP4A phosphatase activity with JMS-053 decreases STAT3 activation and increases SHP-2 phosphatase and p38 kinase phosphorylation activation in ovarian cancer cells. The newly developed JMS-053 resistant ovarian cancer cells should provide useful tools to further probe the role of PTP4A phosphatase in ovarian cancer cell survival and cell signaling.

The drug repositioning procedure can effectively identify new therapeutic tools for ESCC. Our findings suggest that nilotinib and teniposide are efficacious inhibitors of ILK and thus have potential to target ILK-mediated signaling pathways for management of ESCC.

No abstract available

We also screened for susceptibility between the high-risk and low-risk groups and showed that patients in the high-risk group were more sensitive to talazoparib-1259, camptothecin-1003, vincristine-1818, Azd5991-1720, Teniposide-1809, and Nutlin-3a (-) -1047.Finally, we examined the expression of OLR1, SCN1B, and PDE4B genes in HNSCC pathological tissues and validated that these genes could be used to predict the prognosis of HNSCC. It is a non-invasive genomic characterization prediction method that has shown satisfactory and effective performance in predicting patient survival outcomes and treatment response. More interdisciplinary areas combining medicine and electronics will be explored in the future.

Finally, we proposed five KG-guided repurposable drug molecules (imatinib, regorafenib, pazopanib, teniposide, and dexrazoxane) for TNBC through network pharmacology and molecular docking analyses. These drug molecules also showed significant binding performance with some cancer-related PTM-sites (phosphorylation, succinylation, and ubiquitination) of top-ranked four key proteins (EGFR, AURKB, BIRC5, and TOP2A). Therefore, the findings of this computational study may play a vital role in early diagnosis and therapies against TNBC by wet-lab validation.

Downregulation of the A receptor decreases MRP3 expression and chemosensibilizes GSCs treated with teniposide under hypoxia. These data suggest that hypoxia-dependent activation of A adenosine receptor promotes survival of GSCs through MRP3 induction.

By combination of two therapies approved by the Food and Drug Administration, we safely stimulated an immunogenic, T cell-inflamed HCC TME, leading to further sensitization of tumors to anti-PD-1 immunotherapy. These findings might enrich therapeutic strategies for advanced HCC andwe can attempt to improve the response rates of patients with HCC to PD-1 Ab by enhancing DNA-activated STING signaling through effective tumor reoxygenation.

The Paraguayan toad recipe contains metabolites from the toad ingredient, including alkaloids and bufadienolide derivatives. The CE lacks cytotoxic effects alone or in combination with chemotherapeutics. However, it increases mitochondrial bioenergetics and inhibits the cancer cell migration in an AMPK-dependent manner in BC cells. This is the first report of the in vitro anticancer effect of a traditional Rhinella sp. toad preparation based on Mbya tradition.

The sensitivity of each group of cells to the chemotherapeutic drugs teniposide (VM-26) and carmustine (BCNU) was also detected by the MTT method. In contrast, the stemness phenotype of tumor cells with downregulated Notch1 gene expression was significantly suppressed, while the sensitivity to VM-26 and BCNU was increased. High Notch1 expression increased the stemness of SGC-7901 cells and decreased the sensitivity of SGC-7901 cells to chemotherapeutic drugs.

DFF40 deficient cells show chemoresistance to antimetabolites (e.g. methotrexate, 6-mercaptopurine and cytarabine) and surprisingly, they are more sensitive to TOP2 inhibitors (e.g. etoposide and teniposide). The abolition of DFF40 expression in Jurkat cells significantly impairs histone H2AX phosphorylation following etoposide and cytarabine treatments. Our findings suggest that DFF40 is a novel key target in cancer cell resistance that potentially regulates genomic stability.

Among the predicted repurposable drugs, topoisomerase II inhibitors (doxorubicin, teniposide, idarubicin, mitoxantrone, and epirubicin) presented a high potential to reverse rectal cancer gene expression signatures. Finally, we observed significant TOP2A copy number gains and increased expression in independent cohorts of rectal cancer patients. These findings can be translated into clinical practice to evaluate TOP2A status for targeted and personalized therapies based on topoisomerase II inhibitors in rectal cancer patients.

Screening of 107 FDA-approved anti-cancer drugs identified nine compounds with potent activity against IDHmt gliomas, including three compounds with favorable pharmacokinetic characteristics for CNS penetration: teniposide, omacetaxine mepesuccinate, and marizomib. Our twelve IDH-mutant cell cultures show high similarity to the parental tissues and offer a unique tool to study the biology and drug sensitivities of high-grade IDHmt gliomas in vitro. Our drug screening studies reveal lack of sensitivity to IDHmt inhibitors, but sensitivity to a set of nine available anti-cancer agents.

The expression of Immunosuppressive cytokines DNMT1/EZH2 was up-regulated in A-HCC patients, and teniposide may be a potential therapeutic drug for A-HCC. Our model redefined A-HCC prognosis risk, identified potential m6As linking tumour progress and immune regulations and selected possible therapy target, thus promoting understanding and clinical applications about A-HCC.

P2, N=94, Completed, St. Jude Children's Research Hospital | Active, not recruiting --> Completed

Therapy of malignant glioma depends on the induction of O-methylguanine by the methylating agent temozolomide (TMZ). In contrast to BV6 and venetoclax, AT406, embelin, and TMZ itself, teniposide and the PARP inhibitor pamiparib did not increase cell death in senescent cells. Based on these data, we suggest that BV6 and venetoclax act as senolytic agents in glioblastoma cells upon TMZ exposure.

P2, N=94, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Apr 2021 --> Jul 2021 | Trial primary completion date: Apr 2021 --> Jul 2021