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Resumo
No cancro do pulmão, ainda não se obteve sobrevivência expressiva dos doentes que se apresentam em estádios não cirúrgicos. Os doentes com carcinoma de não pequenas células são tratados com platina e outros fármacos, para os quais se podem caracterizar actualmente marcadores preditivos de resposta terapêutica.
Procedeu-se a uma revisão da literatura, tendo como alvo o papel dos genes ERCC1 e RRM1 na resposta à quimioterapia baseada na platina e na gemcitabina. Actualmente, a expressão destes genes é encarada como preditiva de resposta à quimioterapia em doentes com adenocarcinomas e carcinomas epidermóides, orientando a terapêutica personalizada.
Dados publicados demonstram a utilidade da quimioterapia individualizada, de acordo com os níveis individuais de ERCC1. Estes também são influenciados por variabilidade genética. Assim, a presença de certos polimorfismos, como são os códãos 118 C/T e C8092A, parecem estar relacionados com a carcinogénese, resistência aos citostáticos, tempo de sobrevida e até com o prognóstico.
Estudos clínicos e laboratoriais demonstraram também que a elevada expressão do gene RRM1 no NSCLC tem impacto no fenótipo do tumor e na resposta variável à quimioterapia. Doentes submetidos a ressecção cirúrgica, cujos tumores apresentavam expressão aumentado do gene RRM1, têm maior sobrevivência do que os doentes com baixa expressão. No entanto, os doentes com NSCLC avançado sujeitos a quimioterapia com gemcitabina e cisplatina apresentam um pior prognóstico se o tumor apresentar expressão aumentada do gene RRM1.
Palavras-chave:
Carcinoma do pulmão de células não pequenas
RRM1
ERCC1
Abstract
In lung cancer, expressive survival has not yet been achieved in non surgical stages. Non-small cell lung cancer (NSCLC) patients are treated with platinum and other drugs. To choose these agents we can actual ly define predictive biomarkers to preview therapeutic response.
A literature revision was done in order to define the role of ERCC1 e RRM1 genes in the response to chemotherapy based in platinum and gemcitabine respectively. The expression of these genes is faced as a predictive marker to the chemotherapy response in patients with adenocarcinomas and squamous cell carcinomas, providing a personalized therapy.
Published data supports this behaviour and is useful to individualize therapy accordingly to individual levels of ERCC1 which are modified by genetic mutations. Polymorphisms in codons 118 C/T and C8092A, seem to influence the carcinogenesis, cytostatic resistance, survival and even the prognosis.
Clinical and laboratorial trials showed that high expression of RRM1 gene in NSCLC has impact in the tumoral phenotype. Patients having done surgical ressection and presenting high expression of RRM1 have better survival than those with lower expression. However, patients with advanced NSCLC and treated with chemotherapy with gemcitabine and cisplatin appear to have a poor outcome if the tumor express elevated levels of RRM1 gene.
Key-words:
Non-small cell lung cancer
RRM1
ERCC1
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