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Antibody–drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of cytotoxic agents. The technology to develop these agents has improved in past years, but toxicity remains a key issue. This Review provides a broad overview of the recent advances and challenges in ADC development for cancer treatment.
Substituting a hydrogen atom with its heavy isotope deuterium may improve the pharmacokinetic and/or toxicity profile of a drug compared with its non-deuterated counterpart. This article highlights milestones in the field of deuteration in drug discovery and development, and discusses recent examples of its application, which have shifted towards deuteration of novel drug candidates instead of developing deuterated analogues of marketed drugs.
Many diseases involve reduced or absent levels of a particular protein and would benefit from therapies that increase gene expression. In their Review, Khorkova et al. discuss the growing range of RNA-targeted therapies in development that aim to boost gene expression, including nucleic acid-based therapeutics targeting the complex regulatory network of non-coding RNA species.
There have been significant recent advances in the development of single-cell technologies, providing remarkable opportunities for drug discovery and development. Here, Ferran and colleagues discuss how single-cell technologies, primarily single-cell RNA sequencing methods, are being applied in the drug discovery pipeline, from target identification to clinical decision-making. Ongoing challenges and potential future directions are discussed.
Since the COVID-19 pandemic began, many potential therapeutics that target SARS-CoV-2 and/or human proteins to control viral infection have been investigated, with a few receiving authorization by regulatory agencies. This Review article summarizes progress with COVID-19 drug discovery, and discusses the lessons learned about aspects such as drug repurposing, disease models and clinical development strategies.
Drugs that target angiogenic factors such as vascular endothelial growth factor (VEGF) are approved for clinical use in oncology and ophthalmology, but challenges remain. Cao et al. discuss strategies to enhance therapeutic efficacy, overcome drug resistance, define biomarkers and develop next-generation agents for other diseases.
Improving medication adherence is recognized as one of the most impactful and cost-effective strategies for improving the health of the general population. Here, Baryakova and colleagues assess the potential of next-generation drug delivery systems to mitigate many common impediments to adherence and discuss the impact that drug delivery systems have had across different disease types.
Galectins are glycan-binding proteins with broad roles in physiological and pathological processes. Here, Rabinovich and colleagues discuss the therapeutic relevance of galectins to cancer and fibrosis and review the various strategies to target galectins and their progress in clinical trials.
Dysregulated protein phosphorylation is implicated in numerous human diseases, but targeting protein phosphates has traditionally proved challenging. Here, Stanford and Bottini provide an overview of protein phosphatase families, focusing on their roles in autoimmunity and tumour immunity. Emerging strategies to tackle these targets and agents in development are assessed.
