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Novos fármacos no sarcoma de Ewing
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Os doentes com Sarcoma de Ewing (EWS), neoplasia maligna mesenquimatosa caracterizada pela translocação específica t(11;22) e pela proteína de fusão EWSR1-FLI1, não têm tido um aumento muito significativo da sua sobrevivência nos últimos anos apesar dos avanços científicos. A terapêutica consiste na cirurgia e/ou radioterapia, sendo sempre recomendada quimioterapia antes e após as técnicas de controlo local. A escolha do tratamento local depende da possibilidade de excisão com margens seguras, da potencial perda funcional e do tamanho tumoral, entre outros fatores.
Neste estudo pretende-se fazer uma revisão da literatura sobre este subtipo de sarcoma, dando particular relevo à quimioterapia e novas terapêuticas-alvo. Os esquemas de quimioterapia têm vindo a ser alterados ao longo dos anos, de acordo com os resultados dos ensaios clínicos. Atualmente, os principais esquemas utilizam vincristina, ifosfamida, doxorrubicina, etoposido, dactinomicina e ciclofosfamida, em combinações e sequências diferentes. A investigação da biologia molecular e celular do EWS levou à descoberta de potenciais alvos terapêuticos. Vários fármacos dirigidos a estes alvos estão a ser investigados, alguns já em ensaios clínicos, outros apenas com estudos pré-clínicos realizados. Está também a ser pesquisada a presença de biomarcadores que permitam prever a resposta terapêutica. Alguns destes fármacos, como por exemplo, os fármacos anti-IGF-1R, têm mostrados resultados muito promissores, mas aguardam-se mais estudos.
Ewing sarcoma (EWS) is a mesenquimatous malignant neoplasm characterized by the specific translocation t(11;22) and by the fusion protein EWSR1-FLI1. Patients with EWS have not had a significant increase in their overall survival in these last years, despite increasing investigation. Treatment is based on chemotherapy before and after local control approaches, that is, surgery and/or radiotherapy. The choice of the most appropriate local treatment depends on the tumor size, the probability to obtain negative margins and the potential functional loss, among other factors. This study intends to review the literature on this subtype of sarcoma, with particular regard to chemotherapy and targeted therapies. The chemotherapy regimens have changed over the years, following the results of clinical trials. Currently, the main chemotherapy regimens use vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide, and dactinomycin, in different combinations and sequences. Basic research on the molecular and cellular biology of EWS has led to the discovery of potential therapeutic targets. Several drugs directed at these targets are currently under investigation. While some of them are already being tested in clinical trials, others have only now completed preclinical studies. Several potential biomarkers are also being evaluated to predict response to therapy. Some of these drugs, such as anti-IGF-1R drugs have shown promising results, but further studies are still needed.
Ewing sarcoma (EWS) is a mesenquimatous malignant neoplasm characterized by the specific translocation t(11;22) and by the fusion protein EWSR1-FLI1. Patients with EWS have not had a significant increase in their overall survival in these last years, despite increasing investigation. Treatment is based on chemotherapy before and after local control approaches, that is, surgery and/or radiotherapy. The choice of the most appropriate local treatment depends on the tumor size, the probability to obtain negative margins and the potential functional loss, among other factors. This study intends to review the literature on this subtype of sarcoma, with particular regard to chemotherapy and targeted therapies. The chemotherapy regimens have changed over the years, following the results of clinical trials. Currently, the main chemotherapy regimens use vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide, and dactinomycin, in different combinations and sequences. Basic research on the molecular and cellular biology of EWS has led to the discovery of potential therapeutic targets. Several drugs directed at these targets are currently under investigation. While some of them are already being tested in clinical trials, others have only now completed preclinical studies. Several potential biomarkers are also being evaluated to predict response to therapy. Some of these drugs, such as anti-IGF-1R drugs have shown promising results, but further studies are still needed.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016
Palavras-chave
Sarcoma de Ewing Tratamento farmacológico Terapêutica Oncologia