Related Experiment Video

Updated: Jun 22, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Small-molecule BH3 mimetics to antagonize Bcl-2-homolog survival functions in cancer

Kelly C Goldsmith1, Michael D Hogarty

  • 1The Children's Hospital of Philadelphia, Division of Oncology, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA.

Current Opinion in Investigational Drugs (London, England : 2000)
|June 11, 2009
PubMed

Insights

Cancer cells evade programmed cell death (apoptosis) by altering Bcl-2 homology (BH) proteins. BH3 mimetics offer a strategy to restore apoptosis sensitivity in cancer therapy, particularly in neuroblastoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Cancer cells develop genetic alterations enhancing survival and autonomy.
  • These alterations activate cellular checkpoints, including mitochondrial apoptosis, which cancer cells must bypass.
  • Bcl-2 homology (BH) proteins are key regulators of apoptosis, and their dysregulation is critical in cancer progression.

Purpose of the Study:

  • To review the role of BH proteins in cancer cell survival and apoptosis evasion.
  • To discuss the therapeutic potential of small-molecule BH3 mimetics in restoring apoptosis.
  • To present neuroblastoma as a model for integrating BH3 mimetics into clinical practice.

Main Methods:

  • Literature review of cancer cell biology and apoptosis regulation.
  • Analysis of the role of Bcl-2 homology (BH) proteins in cancer.
  • Discussion of small-molecule BH3 mimetics as therapeutic agents.

Main Results:

  • Cancer cells elevate the threshold for apoptosis activation, creating a survival bias.
  • The apoptotic machinery's integrity is largely preserved in cancer, suggesting susceptibility to targeted therapies.
  • Emerging evidence supports BH3 mimetics in restoring cancer cell sensitivity to death signals.

Conclusions:

  • Targeting BH proteins with BH3 mimetics represents a promising therapeutic strategy for cancer.
  • BH3 mimetics can re-sensitize cancer cells to apoptotic stressors, overcoming treatment resistance.
  • Neuroblastoma serves as a relevant model for the clinical application of BH3 mimetics in pediatric oncology.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

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

Published on: May 15, 2019

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 specific...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...