RESUMO
As one of the life-threatening diseases involving multi-step genetic and epigenetic disorders, cancer has long been a dynamic research area for siRNA-based therapy as half of the current siRNA-based clinical trials are involved in oncology. However, despite consistent enthusiasm in the academic world, siRNA-based cancer treatment still faces obstacles and difficulties in clinical development. In this article, we discuss key challenges facing siRNA-based cancer treatment revealed from recent clinical and preclinical studies, including chemical modification, tumour penetration, endosomal escape, target selection and off-target effects. In addition, opportunities and avenues for translating siRNA technology from bench to oncologic clinics are explored.
Assuntos
Inativação Gênica , Terapia Genética , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/terapia , RNA Interferente Pequeno/genética , Animais , Humanos , Proteínas de Neoplasias/genética , Neoplasias/genéticaRESUMO
Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy.
Assuntos
Antineoplásicos/uso terapêutico , Descoberta de Drogas/métodos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Humanos , Modelos Biológicos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Processos Estocásticos , Resultado do Tratamento , Microambiente TumoralRESUMO
Cancer as a genetic disorder is one of the leading causes of death worldwide. Conventional anticancer options such as chemo- and/or radio-therapy have their own drawbacks and could not provide a cure in most cases at present. More effective therapeutic strategies with less side effects are urgently needed. Aptamers, also known as chemical antibodies, are single strand DNA or RNA molecules that can bind to their target molecules with high affinity and specificity. Such site-specific binding ability of aptamers facilitates the delivery and interaction of exogenous nucleic acids with diseased genes. Thus, aptamer-guided gene therapy has emerged as a promising anticancer strategy in addition to the classic treatment regimen. Aptamers can directly deliver anti-cancer nucleic acids, e.g. small interfering RNA, micro RNA, antimicroRNA and small hairpin RNA, to cancer cells or function as a targeting ligand to guide nanoparticles containing therapeutic nucleic acids. This review focuses on recent progress in aptamer-mediated gene therapy for the treatment of hepatocellular carcinoma and other types of cancers, shedding light on the potential of this novel approach of targeted cancer gene therapy.
Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Técnicas de Transferência de Genes , Terapia Genética , Neoplasias/terapia , Aptâmeros de Nucleotídeos/genética , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/uso terapêutico , Humanos , MicroRNAs/uso terapêutico , Neoplasias/genéticaRESUMO
Deposition of amyloid-ß (Aß) peptides in the brain is a central event in the pathogenesis of Alzheimer's disease (AD), which makes Aß peptides a crucial target for therapeutic intervention. Significant efforts have been made towards the development of ligands that bind to Aß peptides with a goal of early detection of amyloid aggregation and the neutralization of Aß toxicity. Short single-stranded oligonucleotide aptamers bind with high affinity and specificity to their targets. Aptamers that specifically bind to Aß monomers, specifically the 40 and 42 amino acid species (Aß(1-40) and Aß(1- 42)), fibrils and plaques have a great potential for diagnostic applications and the treatment of AD. Herein, we review the aptamers that bind to the various forms of Aß peptides for use in diagnosis and to inhibit plaque formation.
