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<p>In retinoblastoma (RB), the search for newer therapeutics is a thrust area for better disease management, and there is a lack of in vitro models that recapitulate the clinical scenario. Hence, we aim to establish RB patient-derived spheroid culture and evaluate its utility as an in vitro drug screening model. Initially we employed different media compositions to optimize the spheroid culture establishment. Sanger sequencing and Multiplex ligation dependent probe amplification were done to confirm the <i>RB1</i> genotype of the spheroids. Drug responsiveness was assessed using CellTiter-Glo<sup>®</sup> luminescence-based cytotoxicity assay and correlated with patients clinicopathological details. Spheroids were successfully cultured using DMEM-F12 media with defined growth factors in nine tumors and one vitreous sample. <i>RB1</i> genotyping of spheroids showed the similar mutational landscape as the tumor samples. Based on the in vitro drug responsiveness to carboplatin, five cultures were segregated as chemoresistant in which four of them were clinically known high-risk RB. One of the spheroids was further expanded and used to evaluate the in vitro efficacy of an FDA-approved drug to overcome resistance. Therefore, these RB patient-derived spheroids closely mirroring the clinicopathological features of the patient samples, represent a promising tool for drug screening and personalized RB therapy development.</p>

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Patient-derived spheroid culture: A promising in vitro model for drug screening in retinoblastoma

  • 期刊论文

  • 发表日期：

    2026年3月9日

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  • Rathinavel Sethu Nagarajan,
  • Sekaran Balaji,
  • Usha Kim,
  • Radhakrishnan Shanthi,
  • Gowri Priya Chidambaranathan,
  • Ramprasad Obula Giridhara Gopalan,
  • Ayyasamy Vanniarajan

摘要

In retinoblastoma (RB), the search for newer therapeutics is a thrust area for better disease management, and there is a lack of in vitro models that recapitulate the clinical scenario. Hence, we aim to establish RB patient-derived spheroid culture and evaluate its utility as an in vitro drug screening model. Initially we employed different media compositions to optimize the spheroid culture establishment. Sanger sequencing and Multiplex ligation dependent probe amplification were done to confirm the RB1 genotype of the spheroids. Drug responsiveness was assessed using CellTiter-Glo® luminescence-based cytotoxicity assay and correlated with patients clinicopathological details. Spheroids were successfully cultured using DMEM-F12 media with defined growth factors in nine tumors and one vitreous sample. RB1 genotyping of spheroids showed the similar mutational landscape as the tumor samples. Based on the in vitro drug responsiveness to carboplatin, five cultures were segregated as chemoresistant in which four of them were clinically known high-risk RB. One of the spheroids was further expanded and used to evaluate the in vitro efficacy of an FDA-approved drug to overcome resistance. Therefore, these RB patient-derived spheroids closely mirroring the clinicopathological features of the patient samples, represent a promising tool for drug screening and personalized RB therapy development.