Scholarlink

<p>Bladder cancer (BC) exhibits high inter- and intra-patient heterogeneity, limiting the efficacy of standard treatments and underscoring the need for personalized therapeutic models. We established patient-derived organoids (PDOs) from 31 clinical BC specimens, achieving an 80.65% success rate. These organoids preserved distinct morphological subtypes: solid, hollow, and mixed and retained stable proliferative capacity. Histological and molecular analyses confirmed that PDOs recapitulated key features of the parental tumors, including a hybrid basal-luminal phenotype with elevated CD44, GATA3, and LGR5 expression, and peripheral localization of CK20 and Uroplakin 3&#xa0;A (UPK3A), indicating structural polarity and urothelial differentiation. Functional drug screening of early-passage PDOs revealed heterogeneous responses to standard-of-care (SOC) agents, cisplatin and gemcitabine, as well as the EGFR/HER2 inhibitor lapatinib. Notably, lapatinib enhanced chemosensitivity in a dose-dependent manner, even at reduced concentrations of standard agents. The most effective combinatorial regimens significantly impaired organoid viability and architecture, suggesting a synergistic effect. Drug response variability across PDO lines correlated with patient-specific clinical features, including tumor grade and recurrence status. These results demonstrate that BC PDOs faithfully model tumor heterogeneity and offer a robust platform for individualized drug response profiling. Our findings support the utility of PDOs for preclinical drug evaluation and precision oncology, particularly in identifying effective combination therapies such as lapatinib-enhanced chemotherapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Patient-derived organoids as a predictive platform for drug sensitivity in bladder cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月27日

查看全文
  • Shirin Hekmatirad,
  • Fatemeh Gholizadeh,
  • Saeed Montazeri,
  • Laleh Sharifi,
  • Mohammad Reza Nowroozi,
  • Amir Ali Hamidieh,
  • Mohammad Hosein Yazdi,
  • Mahsa Mollapour Sisakht

摘要

Bladder cancer (BC) exhibits high inter- and intra-patient heterogeneity, limiting the efficacy of standard treatments and underscoring the need for personalized therapeutic models. We established patient-derived organoids (PDOs) from 31 clinical BC specimens, achieving an 80.65% success rate. These organoids preserved distinct morphological subtypes: solid, hollow, and mixed and retained stable proliferative capacity. Histological and molecular analyses confirmed that PDOs recapitulated key features of the parental tumors, including a hybrid basal-luminal phenotype with elevated CD44, GATA3, and LGR5 expression, and peripheral localization of CK20 and Uroplakin 3 A (UPK3A), indicating structural polarity and urothelial differentiation. Functional drug screening of early-passage PDOs revealed heterogeneous responses to standard-of-care (SOC) agents, cisplatin and gemcitabine, as well as the EGFR/HER2 inhibitor lapatinib. Notably, lapatinib enhanced chemosensitivity in a dose-dependent manner, even at reduced concentrations of standard agents. The most effective combinatorial regimens significantly impaired organoid viability and architecture, suggesting a synergistic effect. Drug response variability across PDO lines correlated with patient-specific clinical features, including tumor grade and recurrence status. These results demonstrate that BC PDOs faithfully model tumor heterogeneity and offer a robust platform for individualized drug response profiling. Our findings support the utility of PDOs for preclinical drug evaluation and precision oncology, particularly in identifying effective combination therapies such as lapatinib-enhanced chemotherapy.