Related Experiment Video
Updated: Sep 26, 2026

Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
Published on: September 5, 2018
Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for
Mohamed K Diab1, Asmaa S A Yassen2,3, Sherif Ashraf Fahmy4
1Pest Physiology Department, Plant Protection Research Institute, Agricultural Research Center Giza 12311 Egypt.
Abstract:
Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that couple chromatin acetylation to oncogenic and immune-regulatory gene transcription, making them attractive targets for combination with immune checkpoint inhibitors (ICIs) in precision oncology. This review synthesizes current mechanistic, medicinal-chemistry, and translational evidence on BET-ICI combination strategies. We describe how BET blockade reshapes tumor chromatin architecture, suppresses PD-L1 expression, and enhances antigen presentation, thereby increasing tumor susceptibility to immune-mediated attack. We further summarize preclinical efficacy data for BET-ICI combinations, including systems-biology and agent-based computational models that predict substantially greater tumor-volume reduction with combination regimens relative to monotherapy in selected preclinical settings; however, early-phase clinical experience with these combinations remains limited and has not yet reproduced this magnitude of benefit. Beyond the mechanism, we review the medicinal chemistry underlying BET inhibitor design and the emerging landscape of BET-ICI hybrid and conjugate therapeutics, distinguishing combinations with direct experimental support from conceptual pairings that remain hypothesis-generating. Finally, we discuss how systems biology and generative, AI-guided molecular design may inform resistance-mechanism prediction, toxicity mitigation, and biomarker-guided, patient-specific compound selection. Collectively, this review outlines a framework for how the convergence of epigenetic reprogramming, immune modulation, and generative bioorganic chemistry could inform the rational design of next-generation BET-ICI combination therapeutics.
Related Concept Videos
Tumor Immunotherapy
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...