RESUMEN
Oncogenes are ideal targets for therapies which down-regulate gene expression. However, effective modalities for altering gene expression in vivo have thus far proven to be elusive. Whilst there has been recent success with small molecule inhibitors of oncoprotein function, evolution of resistance to these agents has been observed in the clinical setting, indicating the need for combinations of therapies for cancer treatment. Strategies for in vivo gene down-regulation still hold promise for the treatment of cancer. The technologies relevant to such therapeutic strategies are discussed in terms of molecular action, delivery and choice of target gene. Consideration is given to the pre-clinical and clinical efficacy these agents have demonstrated to date.
Asunto(s)
Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias/tratamiento farmacológico , Oncogenes/fisiología , Animales , Vectores Genéticos , Humanos , Neoplasias/genética , Oligonucleótidos Antisentido/farmacología , Interferencia de ARN , ARN Catalítico/genética , ARN Catalítico/metabolismo , ARN Catalítico/farmacologíaRESUMEN
Mouse model systems which allow bone marrow reconstitution can be used to analyse genetically programmed leukemia. The original and most widely used system is that of post 5-fluorouracil mouse hematopoietic stem cells (HSC) into lethally irradiated syngeneic mice. Another more recent system allows analysis of human HSCs in the NOD-SCID mouse. Both systems are discussed as models for analysis of gene induced leukemia.