2. Academic Validation
  3. Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases

Application of Drug Testing Platforms in Circulating Tumor Cells and Validation of a Patient-Derived Xenograft Mouse Model in Patient with Primary Intracranial Ependymomas with Extraneural Metastases

  • Diagnostics (Basel). 2023 Mar 24;13(7):1232. doi: 10.3390/diagnostics13071232.
Muh-Lii Liang 1 2,  Ting-Chi Yeh 2 3,  Man-Hsu Huang 4,  Pao-Shu Wu 5 6,  Shih-Pei Wu 7,  Chun-Chao Huang 2 8,  Tsung-Yu Yen 9 10,  Wei-Hsin Ting 2 11,  Jen-Yin Hou 3,  Jia-Yun Huang 12,  Yi-Huei Ding 13,  Jia-Huei Zheng 14,  Hsi-Che Liu 2 3,  Che-Sheng Ho 2 12,  Shiu-Jau Chen 1 2,  Tsung-Han Hsieh 14
Affiliations

Affiliations

  • 1 Department of Neurosurgery, MacKay Memorial Hospital, Taipei 104, Taiwan.
  • 2 Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan.
  • 3 Division of Pediatric Hematology-Oncology, Department of Pediatrics, Mackay Children's Hospital, Taipei 104, Taiwan.
  • 4 Department of Pathology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan.
  • 5 Department of Pathology, MacKay Memorial Hospital, Taipei 104, Taiwan.
  • 6 Mackay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan.
  • 7 CancerFree Biotech, Ltd., Taipei 114, Taiwan.
  • 8 Department of Radiology, MacKay Memorial Hospital, Taipei 104, Taiwan.
  • 9 Department of Radiation Oncology, MacKay Memorial Hospital, Taipei 104, Taiwan.
  • 10 Hospice and Palliative Care Center, MacKay Memorial Hospital, Taipei 104, Taiwan.
  • 11 Department of Pediatric Endocrinology, MacKay Children's Hospital, Taipei 104, Taiwan.
  • 12 Division of Pediatric Neurology, Department of Pediatrics, MacKay Children's Hospital, Taipei 104, Taiwan.
  • 13 Department of Medical Research, Mackay Memorial Hospital, Tamshui Branch, New Taipei City 251, Taiwan.
  • 14 Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan.
PMID: 37046450 DOI: 10.3390/diagnostics13071232
Abstract

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and Adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

Keywords

circulating tumor cells; drug screening; ependymoma; extraneural metastasis; patient-derived xenograft.

Figures
Products