Nucleic acid-based drugs for patients with solid tumours
Cet article analyse le développement, l'activité clinique, les mécanismes d'action, la tolérabilité et l'efficacité des traitements à base d'acides nucléiques viraux ou non viraux chez les patients atteints d'une tumeur solide, décrit les effets du microenvironnement tumoral sur ces traitements lors de leur administration systémique ou localisée puis examine les principaux résultats des essais cliniques et des tests précliniques en cours ainsi que les considérations concernant la fabrication et/ou la stabilité des prochains médicaments à base d'acides nucléiques
The treatment of patients with advanced-stage solid tumours typically involves a multimodality approach (including surgery, chemotherapy, radiotherapy, targeted therapy and/or immunotherapy), which is often ultimately ineffective. Nucleic acid-based drugs, either as monotherapies or in combination with standard-of-care therapies, are rapidly emerging as novel treatments capable of generating responses in otherwise refractory tumours. These therapies include those using viral vectors (also referred to as gene therapies), several of which have now been approved by regulatory agencies, and nanoparticles containing mRNAs and a range of other nucleotides. In this Review, we describe the development and clinical activity of viral and non-viral nucleic acid-based treatments, including their mechanisms of action, tolerability and available efficacy data from patients with solid tumours. We also describe the effects of the tumour microenvironment on drug delivery for both systemically administered and locally administered agents. Finally, we discuss important trends resulting from ongoing clinical trials and preclinical testing, and manufacturing and/or stability considerations that are expected to underpin the next generation of nucleic acid agents for patients with solid tumours.
Nature Reviews Clinical Oncology , résumé, 2024