Related Experiment Video

Updated: Dec 14, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.6K

Targeting BET bromodomain proteins in cancer: The example of lymphomas

Filippo Spriano1, Anastasios Stathis2, Francesco Bertoni3

  • 1Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Pharmacology & Therapeutics
|July 22, 2020
PubMed

Insights

Targeting Bromo- and Extra-Terminal domain (BET) proteins shows promise in cancer treatment. Enhancing BET inhibitors through novel compounds and combination therapies may improve clinical efficacy against various malignancies.

Area of Science:

  • Epigenetics and Cancer Biology
  • Molecular Oncology
  • Pharmacology

Background:

  • Bromo- and Extra-Terminal domain (BET) proteins are key epigenetic regulators involved in transcription.
  • Dysregulation of BET proteins (BRD2, BRD3, BRD4, BRDT) is implicated in various cancers.
  • BET inhibition is a promising anti-cancer strategy with significant preclinical data.

Purpose of the Study:

  • To review laboratory and early clinical trial data on BET protein inhibition, using lymphoma as a model.
  • To discuss strategies for enhancing the efficacy of BET-targeting therapies.
  • To explore potential combination treatments and address resistance mechanisms and toxicity.

Main Methods:

  • Review of preclinical data on BET inhibitors in various tumor types.
  • Analysis of early-phase clinical trial outcomes for BET-targeted agents.
  • Exploration of combination strategies with other therapeutic modalities.

Main Results:

  • While preclinical data for BET inhibition are highly encouraging, clinical results have been moderate.
  • Lymphoma serves as a case study for evaluating BET targeting efficacy.
  • Potential for improved outcomes exists through novel compound development and combination therapies.

Conclusions:

  • BET inhibitors represent a valuable therapeutic avenue in oncology, particularly for hematological malignancies.
  • Overcoming current limitations requires developing next-generation BET inhibitors and exploring rational combination strategies.
  • Combinations with signaling pathway inhibitors, BCL2 inhibitors, DNA damage response agents, epigenetic drugs, or immunotherapy warrant further investigation to improve clinical responses and manage resistance and toxicity.
Keywords:
BETBRD2BRD4DNA damage responseJQ1MYCPROTACbromodomaindiffuse large B-cell lymphomaepigeneticsimmuno-oncologylymphoma

More Related Videos

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

10.8K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.7K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...
5.7K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.5K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
3.7K