Dados do Trabalho

Título

CHALLENGES IN RHABDOMYOSARCOMA TREATMENT: TUMOR RESISTANCE PREDICTION IN AN IN VITRO PLATFORM

Introdução

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and requires a multimodal treatment, including chemotherapy. Most patients with low-risk localized RMS can be cured with the current treatments, however, patients with recurrent RMS and metastasis presented a poor prognosis. Establishing an in vitro chemoresistance platform aiming at identifying ineffective agents to which the tumor is resistant might allow improving therapeutic outcomes.

Objetivo

Our study aims to validate the efficacy of an in vitro chemoresistance platform to demonstrate resistance in Rhabdomyosarcoma.

Métodos

Two sarcoma cell lines (SK-ES-1 (anaplastic osteosarcoma) and HT-1080 (fibrosarcoma)) were used to confirm the efficacy of the platform. Patients diagnosed with RMS were included. Fresh tumor samples were collected and dissociated to obtain the tumor cells. The tumor cells were cultured in the chemoresistance platform with cytotoxic drug, and after 72h, cell viability was evaluated. The test result is defined based on cell viability as low (< 40%), medium (40-60%), and high (> 60%) resistance.

Resultados

The sarcoma cell lines confirmed the efficacy of the platform. The anaplastic osteosarcoma presented a low resistance profile, while the fibrosarcoma exhibited high resistance to most tested cytotoxic drugs. Samples from 2 patients with RMS were included. Patient one was a one-year-old male diagnosed with an RMS in head/neck region, and patient two was a three-year-old female with RMS in the leg. Both patients underwent surgery followed by adjuvant chemotherapy and radiotherapy. Patient one received ifosfamide, doxorubicin, vincristine, and dactinomycin and experienced a local recurrence 8 months after the surgery. Patient two received ifosfamide, doxorubicin, and vincristine and remains disease-free. In the chemoresistance platform, the tumor sample from patient one displayed high resistance rates to vincristine and doxorubicin, while the tumor sample from patient two presented a low-intermediate resistance profile to the same drugs.

Conclusões

This preliminary finding highlights the technique success of the in vitro chemoresistance platform in demonstrating distinct tumor resistance profiles in patients with RMS, and suggests a potential association between the platform result and clinical outcome.

Palavras-chave

Sarcoma, drug therapy, drug resistance