Assuntos
Aberrações Cromossômicas , Células Clonais , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Idoso , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , MasculinoAssuntos
Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/genética , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Neoplasias Testiculares/complicações , Neoplasias Testiculares/genética , Idoso , Humanos , MasculinoAssuntos
Imunidade Celular/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Linfócitos T/imunologia , Adolescente , Adulto , Benzamidas , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Criança , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mesilato de Imatinib , Imunização , Interferon-alfa/uso terapêutico , Linfócitos T/efeitos dos fármacosRESUMO
Surgery has been the mainstay of renal cell carcinoma (RCC) treatment for resectable tumours. In stages I-III disease, nephrectomy is the standard of care and may be curative. Historically, patients presenting with stage IV disease may achieve improved survival with debulking nephrectomy, which is commonly performed prior to systemic therapy. The response rate of immunotherapy is low, with a smaller percentage exhibiting complete remission upon treatment. Therefore, new therapeutic approaches against metastatic RCC are necessary. Recently, molecular mechanisms responsible for the proliferation of RCC have been identified, and molecular targeted therapy has developed. Clear cell RCC commonly features mutation or inactivation of the von Hippel- Lindau (VHL) gene and resultant over-expression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and has been shown to prolong progression-free survival (PFS) when used in second-line treatment. This review describes recent advances in molecular targeted therapy for metastatic RCC, focusing on chemical structure and mechanism of action of VEGFR and mTOR inhibitors.