patupilone (EPO 906)

Moreover, the abundant presence of ZHER2:342 on the surface effectively enhances the targeting capacity and tumor accumulation of the drug. Z-E ADCN can be internalized by cancer cells via HER2 receptor-mediated endocytosis followed by Epo B release in response to high levels of ROS, resulting in excellent anticancer efficacy in HER2-positive tumor models.

P2, N=349, Active, not recruiting, National Cancer Institute (NCI)

Notably, the low-risk group exhibited higher sensitivity to epothilone.B, metformin, and tipifarnib compared to the high-risk group. The nomogram incorporating these factors demonstrated improved performance in predicting gastric cancer prognosis. Our study established risk features derived from GARGs that hold potential clinical utility in prognostic assessment and immune therapy response evaluation of gastric cancer patients.

P1, N=22, Active, not recruiting, National Cancer Institute (NCI)

The current study established a powerful prognostic DISULncSig signature for LUAD that was also valid for most pan-cancers. This signature could serve as a potential target for immunotherapy and might help the more efficient application of drugs to specific populations.

The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC4) and estradiol 17 β-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.

Epothilone derivatives have been recognized as one of the most powerful anticancer drugs towards solid tumors, for their unique affinity to bind with β-tubulin microtubule arrays, stabilizing their disassembly, causing cell death...The purified A. fumigatus epothilone had a significant activity towards HepG2 (IC 0.98 μg/ml), Pancl (IC 1.5 μg/ml), MCF7 (IC 3.7 μg/ml) and WI38 (IC 4.6 μg/ml), as well as a strong anti-tubulin polymerization activity (IC 0.52 μg/ml) compared to Paclitaxel (2.0 μg/ml). The effect of A. fumigatus epothilone on the immigration ability of HepG2 cells was assessed, as revealed from the wound closure of the monolayer cells that was estimated by ~ 63.7 and 72.5%, in response to the sample and doxorubicin, respectively, compared to negative control. From the Annexin V-PI flow cytometry results, a significant shift of the normal cells to the apoptosis was observed in response to A. fumigatus epothilone by ~ 20 folds compared to control cells, with the highest growth arrest of the HepG2 cells at the G0-G1 stage.

The current study established a powerful prognostic CoCuLncSig signature for LUAD that was also valid for most pan-cancers. This signature could serve as a potential target for immunotherapy and might help the more efficient application of drugs to specific populations.

Additionally, by applying our prediction model, we segregated PC patients into high-risk and low-risk groups, identifying potential benefits of cisplatin, docetaxel, pazopanib, midostaurin, epothilone.B, thapsigargin, bryostatin.1, and AICAR for high-risk PC patients, and metformin, roscovitine, salubrinal, and cyclopamine for those in the low-risk group. This study unveils IFN-γGs related molecular subsets in pancreatic cancer for the first time, shedding light on the pivotal role of IFN-γGs in the progression of PC. Furthermore, we establish an IFN-γGs related prognostic model for predicting the survival of PC, offering a theoretical foundation for exploring the precise mechanisms of IFN-γGs in PC.

Our study provides insights into the mechanisms of immunotherapy resistance in PAC and introduces MBS as a robust metabolism-based indicator for predicting response to immunotherapy and prognosis in patients with PAC. These findings have significant implications for the development of personalized treatment strategies in patients with PAC and highlight the importance of considering metabolic pathways and immune infiltration in TME regulation.

The IC values of 12 chemotherapeutic drugs, including epothilone.B, JNK.inhibitor.VIII, and AKT.inhibitor.VIII, significantly differed between the two risk groups...In addition, KRT8 and TFAP2A were highly expressed, while GATA2 and LMBRD1 were poorly expressed in tumor tissues. Four key prognostic biomarkers-GATA2, TFAP2A, LMBRD1, and KRT8-were used to construct a significant prognostic model for LUAD patients.

Based on cuproptosis-related lncRNAs, we constructed and validated a novel risk signature that may be used to predict immunotherapy efficacy and prognosis in LUAD patients.

Treatments with BI.2536, Epothilone.B, Gemcitabine, Mitomycin.C, Obatoclax. Mesylate, and Sunitinib may profit high-risk patients...Our data highlight FRGs and CRGs in clinical practice and suggest ferroptosis and cuproptosis may be therapeutic targets for HCC patients. To validate the model's clinical efficacy, more HCC cases and prospective clinical assessments are needed.

Moreover, the NPC patients with high risk were sensitive to chemotherapeutic drugs including axitinib, docetaxel, embelin, epothilone.B, parthenolide, thapsigargin, tipifarnib, vinorelbine. Finally, the expression of ABCC1 and GLS2 was validated in NPC tissues using immunohistochemistry. Together, these results revealed ferroptosis may be a potential biomarker in NPC and representing a promising future direction in prognosis and therapeutic strategy for the treatment of NPC.

In addition, immune function analysis showed that patients in the high-risk cohort had higher TMB and were more sensitive to conventional chemotherapy and targeted drugs including doxorubicin, epothilone B, etoposide, and mitomycin C. We constructed a novel CRL-related risk score model to accurately predict the prognosis of PCa patients. Our results indicate that CRLs are potential targets for drug therapy in PCa and provide a possible new direction for personalized treatment of PCa patients.

Epothilone B (EpoB) is an FDA-approved anti-neoplastic agent used to treat metastatic breast cancer; However, its usage is limited due to its severe peripheral neurotoxicity. Moreover, we demonstrated that in vivo EpoB-induced myelin degradation and neuronal dysfunction were mitigated by SRT1720, a sirtuin1 (SIRT1) activator, and by SRT1720 and mitoquinone mesylate (mitoQ). Our results suggest that ferroptosis elicited by EpoB is caused by mitochondrial damage mediated by SIRT1 inactivation and that ferroptosis causes neural dysfunction following EpoB.

This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma. Tumor-associated macrophages may be derived from cirrhosis and can initiate liver carcinoma. Predictive drugs that target the macrophage-naive CD4 + T cell interaction may help to improve the immunosuppressive microenvironment and prevent immune evasion. The relevant mechanisms need to be further validated in experiments and cohort studies.

The drug sensitivity of oxaliplatin and LDK-378 negatively correlated with ITGAV expression. Ten drugs had lower IC50s in the high-risk group, indicating better antitumor efficacy than in the low-risk group, with epothilone B having the lowest IC50 value...The risk grouping of our model can be used to reveal differences in the tumor immune microenvironment of patients with HCC. Further in-depth study may provide new targets for future treatment.

In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested. Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

P3, N=799, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2021 --> Dec 2022

Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.

Utidelone (UTD1), a novel microtubule stabilizing agent, is an epothilone B analogue which was produced by genetic engineering...Moreover, UTD1 inhibited tumor growth and was more effective and safer compared with paclitaxel and 5-FU in RKO xenograft in nude mice. Taken together, our findings first indicate that UDT1 inhibits tumor growth in CRC xenograft model and may be a promising agent for CRC treatment.

Paclitaxel (PTX) is a commonly used taxane for TNBC, well known to induce mitotic arrest through stabilization of microtubules (MT) leading to an interference with the treadmilling function of MT through the activation of the spindle assembly checkpoint...To accomplish this, we have used an epothilone (Epothilone B) and a vinca alkaloid (Vinblastine), that function by stabilizing and destabilizing the MTs, respectively...Examined together, a better understanding of how APC loss influences chemoresistance in TNBC can lead to more efficient treatments for TNBC patients resistant to taxanes. Given the critical interaction between APC and MTs, this may be an avenue for targeted therapies to overcome taxane resistance.

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2020 --> Dec 2022 | Trial primary completion date: Apr 2020 --> Dec 2021

Prediction results revealed that Ixabepilone, an epothilone B analog for treating breast cancer patients, may target Bcl-2, an oncogene that contributes to tumor progression and therapy resistance by inhibiting apoptosis. In addition, Ixabepilone also decreases Bcl-2 protein expression and induces cytoprotective autophagy in human hepatic carcinoma and glioma cells. In conclusion, this study not only provides a feasible and alternative way exploring new molecular mechanisms of drugs by combing computation DTI prediction, but also reveals an effective strategy to reinforce the antitumor efficacy of Ixabepilone.