ArticleOncogene2021
BET protein degradation triggers DR5-mediated immunogenic cell death to suppress colorectal cancer and potentiate immune checkpoint blockade.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- Reactivating necroptosis in colorectal cancer potentiates chemotherapy and antitumor immune responses.Cancer letters · 2026Article
- Esterase-responsive albumin-binding PROTAC-mediated BRD4 degradation for cancer immunotherapy.Theranostics · 2026Article
- Targeted nano-drug delivery systems for tumor immunotherapy.Journal of pharmaceutical analysis · 2026Review
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models.Cell reports. Medicine · 2025Article
- Harnessing the SPOP E3 Ubiquitin Ligase via a Bridged Proteolysis Targeting Chimera (PROTAC) Strategy for Targeted Protein Degradation.Journal of medicinal chemistry · 2025Article
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- PUMA/RIP3 Mediates Chemotherapy Response via Necroptosis and Local Immune Activation in Colorectal Cancer.Molecular cancer therapeutics · 2024Article
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype.Nature communications · 2023Article
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Inhibition of multiple CDKs potentiates colon cancer chemotherapy via p73-mediated DR5 induction.Oncogene · 2023Article
- Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy.Pharmaceutics · 2023Review
- The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy.Frontiers in immunology · 2023Review
- Review
- Small-Molecule PROTACs for Cancer Immunotherapy.Molecules (Basel, Switzerland) · 2022Review
- Mcl-1 inhibition overcomes BET inhibitor resistance induced by low FBW7 expression in breast cancer.Journal of cellular and molecular medicine · 2022Article
- Research progress in inducing immunogenic cell death of tumor cells.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Bromodomain and extra-terminal domain (BET) family proteins are epigenetic readers that play a critical role in oncogenesis by controlling the expression of oncogenes such as c-Myc. Targeting BET family proteins has recently emerged as a promising anticancer strategy. However, the molecular mechanisms by which cancer cells respond to BET inhibition are not well understood. In this study, we found that inducing the degradation of BET proteins by the proteolysis targeting chimeras (PROTAC) approach potently suppressed the growth of colorectal cancer (CRC) including patient-derived tumors. Mechanistically, BET degradation transcriptionally activates Death Receptor 5 (DR5) to trigger immunogenic cell death (ICD) in CRC cells. Enhanced DR5 induction further sensitizes CRC cells with a mutation in Speckle-type POZ protein (SPOP). Furthermore, DR5 is indispensable for a striking antitumor effect of combining BET degradation and anti-PD-1 antibody, which was well tolerated in mice and almost eradicated syngeneic tumors. Our results demonstrate that BET degradation triggers DR5-mediated ICD to potently suppress CRC and potentiate immune checkpoint blockade. These results provide a rationale, mechanistic insights, and potential biomarkers for developing a precision CRC therapy by inducing BET protein degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.