RESUMO
Radiotherapy is along with surgery and chemotherapy one of the prime treatment modalities in cancer. It is applied in the primary, neoadjuvant as well as the adjuvant setting. Radiation techniques have rapidly evolved during the past decade enabling the delivery of high radiation doses, reducing side-effects in tumour-adjacent normal tissues. While increasing local tumour control, current and future efforts ought to deal with microscopic disease at a distance of the primary tumour, ultimately responsible for disease-progression. This review explores the possibility of bimodal treatment combining radiotherapy with immunotherapy.
Assuntos
Vigilância Imunológica/efeitos da radiação , Imunoterapia , Neoplasias/cirurgia , Radiocirurgia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Efeito Espectador , Antígeno CTLA-4/antagonistas & inibidores , Morte Celular/imunologia , Morte Celular/efeitos da radiação , Terapia Combinada , Fracionamento da Dose de Radiação , Previsões , Humanos , Ipilimumab , Camundongos , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias Experimentais/cirurgia , Neoplasias Experimentais/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Evasão Tumoral/imunologia , Evasão Tumoral/efeitos da radiação , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/antagonistas & inibidoresRESUMO
Gliobastoma multiform (GBM) is the most common and aggressive brain tumor, which is characterized by its infiltrative nature. Current standard therapy for GBMs consists of surgery followed by radiotherapy combined with the alkylating agent temozolomide (TMZ). Recent clinical trials have demonstrated that this chemo-irradiation approach results in a significant increase in survival compared to radiotherapy alone. Nevertheless, due to tumor recurrence, the median survival time is still limited to approximately 15 months. Recently, several studies have focused on aberrant signal transduction in GBM, resistance mechanisms of GBM to TMZ and to radiotherapy. Attention has been focused on molecular targets including phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, protein kinase C (pKC) pathway, Ras/mitogen-activated protein kinase pathway (MAPK), Wnt pathway and intrinsic or extrinsic apoptosis pathways. In addition, research has been directed to radiotherapy and radiosensitizing agents, and cancer gene therapy as well. This article will address several resistance mechanisms of GBM to chemotherapy and radiotherapy and the recent preclinical and clinical studies on targeted therapy.
