Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma

Ye, Dingwei; Liu, Jiyan; Zhou, Aiping; Zou, Qing; Li, Hanzhong; Fu, Cheng; Hu, Hailong; Huang, Jian; Zhu, Shuchai; Jin, Jie; Ma, Lulin; Guo, Jianming; Xiao, Jun; Park, Se Hoon; Zhang, Dahong; Qiu, Xiusong; Bao, Yuanyuan; Zhang, Lilin; Shen, Wei; Bi, Feng

doi:10.1111/cas.14681

Cited by 79 publications

(103 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It remains to be investigated whether NTX or its analogues combined with DOX or CIS can enhance the anti-tumor effect, promote the extrusion of drugs into extracellular space by drug efflux pumps, and even delay the development of drug resistance in UBC without significantly increasing toxicity. We also noticed that previous clinical trials focused on the therapeutic effect of NTX (APL-1202) on NMIBC, while a multicenter study (NCT04813107, Phase I/II) on the combination of NTX with tislelizumab, a monoclonal antibody against programmed cell death protein 1 (PD-1) 45 will be started to assess their efficacy and safety in cisplatin-ineligible MIBC patients. Our previous work found that NTX decreases the levels of myeloid-derived suppressor cells (MDSCs) in UBC-bearing murine model 20 .…”

Section: Discussionmentioning

confidence: 99%

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer

Lin¹,

Sun²,

Sadahira³

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time- and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.

show abstract

Section: Discussionmentioning

confidence: 99%

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer

Lin¹,

Sun²,

Sadahira³

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…In terms of urothelial cancer, anti-PD-1/PD-L1 has become the first-line treatment option [ 177 ]. A retrospective analysis of 270 patients in 10 European institutions treated with ICIs indicated that bone metastases were associated with poor prognosis [ 178 ].…”

Section: Clinical Effects Of Immune Checkpoint Inhibitors To Bone Metastasismentioning

confidence: 99%

“…In another study, 113 Asian patients with local progression or distant metastasis received PD-1 inhibitor tislelizumab treatment. The ORR was 24%, while the impact on bone metastasis was not specifically described [ 177 ].…”

Section: Clinical Effects Of Immune Checkpoint Inhibitors To Bone Metastasismentioning

confidence: 99%

Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

Liu

Wang

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.

show abstract

“…In the treatment of classical Hodgkin lymphoma, tislelizumab was well tolerated with a high ORR of 87.1% ( Song et al, 2019a ). It also provided an OS of 9.8 months in patients with UC ( Ye et al, 2021 ). Those results led to its approval for classical Hodgkin lymphoma and UC in China.…”

Section: Clinical Use Efficacy and Safetymentioning

confidence: 99%

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

2021

View full text Add to dashboard Cite

Over the past decade, diverse PD-1/PD-L1 blockades have demonstrated significant clinical benefit in across a wide range of tumor and cancer types. With the increasing number of PD-1/PD-L1 blockades available in the market, differences between the clinical performance of each of them started to be reported. Here, we provide a comprehensive historical and biological perspective regarding the underlying mechanism and clinical performance of PD-1/PD-L1 blockades, with an emphasis on the comparisons of their clinical efficacy and safety. The real-world evidence indicated that PD-1 blockade may be more effective than the PD-L1, though no significant differences were found as regards to their safety profiles. Future head-to-head studies are warranted for direct comparison between them. Finally, we summarize the yet to be elucidated questions and future promise of anti-PD-1/PD-L1 immunotherapy, including a need to explore novel biomarkers, novel combinatorial strategies, and their clinical use on chronic infection.

show abstract

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 79 publications

References 27 publications

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer

Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

Contact Info

Product

Resources

About