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It has been argued that patents impede the development and access of medicines for tropical diseases such as malaria. However, we believe that intellectual property can be a key tool to enable timely progression of drug development projects involving multiple partners and to ensure equitable access to successful products.
Libraries of functionalized small-molecule fragments that can be screened in whole cells could take phenotypic drug discovery to the next level, providing new opportunities against undertargeted proteins.
The European Medicines Agency's PRIME scheme to accelerate the development of promising drugs that address unmet medical needs has enrolled 19 products in its first year, showing considerable overlap with FDA breakthrough therapy designees but also key differences.
Jay Bradner, President of the Novartis Institutes for BioMedical Research, discusses increased interest in chemical biology and open science at Novartis.
Two PD-1 directed checkpoint inhibitors have recently been approved for squamous cell carcinoma of the head and neck (SCCHN). Further checkpoint inhibitors, as well as other molecularly targeted agents and cytokine-based immunotherapies, are currently in the late-stage pipeline and are poised to change the treatment paradigm for SCCHN.
Human cancers commonly have mutations in epigenetic regulatory genes, and several small molecules that target epigenetic regulators are in clinical trials. Here, Pfister and Ashworth discuss the biological complexity of epigenetic regulation in cancer and provide an overview of inhibitors that target gain-of-function mutations, as well as synthetic lethal approaches to target loss-of-function mutations in epigenetic regulators.
Immune checkpoint blockade is a powerful anticancer approach; however, it only works for some patients. Here, Lesterhuis and colleagues argue that response to immune checkpoint blockade is a critical state transition of a complex system. They discuss recent advances in mathematics and network biology that might facilitate the identification of dynamic biomarkers, which in turn might help distinguish responders from non-responders and determine new targets for combination therapy.
The B cell lymphoma 2 (BCL-2) family of proteins has a key role in regulating apoptosis and is often dysregulated in cancer. This has led to the development of several inhibitors of pro-survival BCL-2 family proteins such as BCL-2, BCL-XLand MCL1, including the BCL-2 inhibitor venetoclax, which has recently gained regulatory approval. Here, Ashkenazi and colleagues discuss the latest progress in developing small-molecule inhibitors of pro-survival BCL-2 family proteins.
Chemogenomic screening is increasingly being applied to expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Here, Jones and Bunnage discuss the principles of the creation and use of chemogenomic libraries, highlighting key examples and their applications, including target identification, drug repositioning and predictive toxicology.
