The regulatory approval of ipilimumab (Yervoy) in 2011 ushered in a new era of cancer immunotherapies with durable clinical effects. Most of these breakthrough medicines are monoclonal antibodies that block protein-protein interactions between T cell checkpoint receptors and their cognate ligands. In addition, genetically engineered autologous T cell therapies have also recently demonstrated significant clinical responses in haematological cancers. Conspicuously missing from this class of therapies are traditional small-molecule drugs, which have previously served as the backbone of targeted cancer therapies. Modulating the immune system through a small-molecule approach offers several unique advantages that are complementary to, and potentially synergistic with, biologic modalities. This Review highlights immuno-oncology pathways and mechanisms that can be best or solely targeted by small-molecule medicines. Agents aimed at these mechanisms--modulation of the immune response, trafficking to the tumour microenvironment and cellular infiltration--are poised to significantly extend the scope of immuno-oncology applications and enhance the opportunities for combination with tumour-targeted agents and biologic immunotherapies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/nrd4596 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Coordinating uncertainty in the political economy of cyber threat intelligence.
Soc Stud Sci
January 2025
King's College London, London, UK.
Cyber threat intelligence firms play a powerful role in producing knowledge, uncertainty, and ignorance about threats to organizations and governments globally. Drawing on historical and ethnographic methods, we show how cyber threat intelligence analysts navigate distinctive types of uncertainty as they transform digital traces into marketable products and services. We make two related contributions and arguments.
View Article and Find Full Text PDFProgress on ancient DNA investigation of Late Quaternary mammals in China.
Yi Chuan
January 2025
State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan 430078, China.
It has been more than 40 years since the beginning of exploring the genetic composition of ancient organisms from the perspective of ancient DNA. In the recent 20 years, with the development and application of high-throughput sequencing technology platforms and the improved efficiency of retrieving highly fragmented DNA molecules, ancient DNA research moved forward to a brand-new era of deep-time paleogenomics. It not only solved many controversial phylogenetic problems, enriched the migration and evolution details of various organisms including humans, but also launched exploration of the molecular responses to climate changes in terms of "whole genomic-big data-multi-species" level.
View Article and Find Full Text PDFBackground: Personality traits, namely higher neuroticism and lower conscientiousness, are predictive of dementia, although the complex relationship has yet to be fully explained. With >60 years of prospectively collected data, the Wisconsin Longitudinal Study (WLS) provides a unique opportunity to thoroughly evaluate this association in a population-based randomly selected cohort. Using a gold-standard diagnostic approach to characterize dementia prevalence, we leverage life course WLS data to examine the association between mid-life personality traits and late-life dementia risk.
View Article and Find Full Text PDFArtificial intelligence and food flavor: How AI models are shaping the future and revolutionary technologies for flavor food development.
Compr Rev Food Sci Food Saf
January 2025
Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai, China.
The food flavor science, traditionally reliant on experimental methods, is now entering a promising era with the help of artificial intelligence (AI). By integrating existing technologies with AI, researchers can explore and develop new flavor substances in a digital environment, saving time and resources. More and more research will use AI and big data to enhance product flavor, improve product quality, meet consumer needs, and drive the industry toward a smarter and more sustainable future.
View Article and Find Full Text PDFHeritable polygenic editing: the next frontier in genomic medicine?
Nature
January 2025
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!