Dados do Resumo

Título

ESTABLISHMENT OF A PRE-CLINICAL STUDY PLATFORM USING PATIENT-DERIVED XENOGRAFTS FOR SOFT TISSUE SARCOMAS

Introdução

Soft tissue sarcomas (STS) are rare neoplasms originating from mesenchymal cells. When diagnosed at advanced and/or metastatic stages, they have a poor prognosis. The lack of effective experimental models for soft tissue sarcomas hampers research into new therapeutic approaches. In this context, creating a Patient-Derived Xenograft (PDX) platform allows for the exploration of the unique characteristics of sarcoma tumor progression.

Objetivo

To establish a PDX model of STS using tumors from patients treated at A.C.C.C., implanted in NSG mice, and using the collected clinical data to build a pre-clinical study platform based on PDX. Additionally, to establish primary cultures and standardize protocols for immortalization and cryopreservation of these cells.

Métodos

To establish the PDX models, 70 patients with soft tissue sarcomas were recruited, covering various histological subtypes, with informed consent obtained through the signing of an Informed Consent Form. The project was analyzed and approved by the Research Ethics Committee under number 2498/18. The collected samples were then used to inoculate tumors into mice, followed by monitoring tumor growth, culturing primary tumor cells, standardizing protocols for immortalization and cryopreservation, and detailed characterization through immunohistochemistry.

Resultados

Out of the 70 patients selected for this study, 33 generated PDX models. A Tissue Microarray (TMA) with the 33 human tumors and their respective PDXs was prepared and characterized using immunohistochemical analyses. Of the 70 samples collected, 21 showed no neoplasia, low grade (histological grade 1), and received neoadjuvant treatment; none of these cases showed tumor growth. After excluding these cases, 49 tumors remained viable, with 33 (67%) successfully generating PDX models. This result is close to what is reported in the literature (76%). Additionally, primary cultures of these tumors were established along with the standardization of protocols for cell immortalization and cryopreservation. Immunohistochemical characterization of key STS diagnostic markers (Desmin, Cytokeratin, CD34, CD99, Myogenin, and S-100) was performed on all cases that generated PDXs and were included in both the patient TMA and the PDX TMA.

Conclusões

The PDX-based platform for sarcomas was successfully established with a good overall engraftment rate of 67%, producing 33 PDX models that are cryopreserved and ready for use in projects investigating tumor biology and for the development and screening of new or repurposed drugs.

Financiador do resumo

CNPq e FAPESP

Palavras Chave

Sarcomas; PDX; Primary Cultures