Research progress on PD-1 and PD-L1 inhibitors in the treatment of metastatic urothelial carcinoma

Tang, Quanqing; Li, Shihao; Huang, Gaozhen; Liu, Hongwei

doi:10.1016/j.intimp.2023.110158

Cited by 5 publications

(1 citation statement)

References 62 publications

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“…Even though response rates can reach up to 60%, it’s far from the ideal. The second-line treatment typically involves immunotherapies, such as inhibitors of PD-1/PD-L1, but these often yield disappointingly low response rates and immune-related adverse effects ( 5 , 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Antibody-drug conjugates in urinary tumors: clinical application, challenge, and perspectives

Li,

Xie,

Deng

et al. 2023

Front. Oncol.

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Urinary tumors primarily consist of kidney, urothelial, and prostate malignancies, which pose significant treatment challenges, particularly in advanced stages. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach, combining monoclonal antibody specificity with cytotoxic chemotherapeutic payloads. This review highlights recent advancements, opportunities, and challenges in ADC application for urinary tumors. We discuss the FDA-approved ADCs and other novel ADCs under investigation, emphasizing their potential to improve patient outcomes. Furthermore, we explore strategies to address challenges, such as toxicity management, predictive biomarker identification, and resistance mechanisms. Additionally, we examine the integration of ADCs with other treatment modalities, including immune checkpoint inhibitors, targeted therapies, and radiation therapy. By addressing these challenges and exploring innovative approaches, the development of ADCs may significantly enhance therapeutic options and outcomes for patients with advanced urinary tumor.

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Section: Introductionmentioning

confidence: 99%

Antibody-drug conjugates in urinary tumors: clinical application, challenge, and perspectives

Li,

Xie,

Deng

et al. 2023

Front. Oncol.

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Synergistic approach to combating triple-negative breast cancer: ddr1-targeted antibody-drug conjugate combined with pembrolizumab

Zhou,

Li,

Zhao

et al. 2024

Journal of Pharmaceutical Analysis

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Molecular classification of high-grade, muscle-invasive urothelial carcinomas and the relationship with CTLA-4 and PD-L1 expression

Pereira,

Mattos,

Martini Filho

et al. 2023

Surg Exp Pathol

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Purpose the aim of the current study was to molecularly classify high-grade, muscle-invasive, urothelial carcinoma of basal, luminal, and p53-like subtypes and to assess their relationship with CTLA-4 and PD-L1 expression. Methods fifty-seven samples from transurethral resections were tested immunohistochemically for CK5/6, CD44, CK20, p63, p53, and CTLA-4/PD-L1. Results about half of the cases presented a basal molecular profile (50.9%), the luminal profile was found in 29.8% and the p53-like profile in 15.8%. Positivity for CTLA-4 occurred in 24 samples (42.1%), with cytoplasmic and membrane expression reported only in neoplastic cells. Of these, 11 were of the luminal subtype, ten were of the basal subtype, and three were of the p53-like subtype. There was an association between CTLA-4 expression and the luminal classification, and an absence of CTLA-4 expression in the basal profile (p = 0.047). PD-L1 expression was found in 12 samples, ten of them classified as the basal subtype (p = 0.036). CTLA-4 and PD-L1 expression were not identified in the same subtypes (p = 0.08), since only one sample was positive for both markers. Conclusions A molecular classification into the subtypes was possible in 96.5% of cases of high-grade, muscle-invasive, urothelial carcinoma using immunohistochemistry. Thus, this type of classification is viable in most surgical pathology laboratories, including those in Brazil’s Unified Health System (known as SUS, the acronym for Sistema Único de Saúde). The expression of CTLA-4 is related to the luminal molecular subtype, while the expression of PD-L1 is related to the basal molecular subtype. CTLA-4 and PD-L1 positivity are mutually exclusive.

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Research progress on PD-1 and PD-L1 inhibitors in the treatment of metastatic urothelial carcinoma

Cited by 5 publications

References 62 publications

Antibody-drug conjugates in urinary tumors: clinical application, challenge, and perspectives

Antibody-drug conjugates in urinary tumors: clinical application, challenge, and perspectives

Synergistic approach to combating triple-negative breast cancer: ddr1-targeted antibody-drug conjugate combined with pembrolizumab

Molecular classification of high-grade, muscle-invasive urothelial carcinomas and the relationship with CTLA-4 and PD-L1 expression

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