Related Experiment Video

Updated: Aug 1, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

The role of caspase-8 in resistance to cancer chemotherapy

P K Kim1, R Mahidhara, D W Seol

  • 1Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|May 7, 2002
PubMed

Insights

Chemotherapy kills cancer cells via apoptosis, a programmed cell death process. Targeting caspase-8 (a key protein in apoptosis) and its inhibitors may overcome drug resistance in malignancies.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Chemotherapeutic agents induce cancer cell death through programmed cell death pathways.
  • Apoptosis, a critical cell death cascade, is executed by caspases, a family of cysteine proteases.
  • Caspase-8 activation is a central event in many apoptosis-inducing signaling pathways.

Purpose of the Study:

  • To explore the role of caspase-8 in chemotherapy-induced apoptosis.
  • To investigate mechanisms of tumor resistance related to apoptosis regulation.
  • To evaluate therapeutic strategies targeting caspase-8 for overcoming drug resistance.

Main Methods:

  • Analysis of caspase-8 expression and its inhibitors in cancer cells.
  • Investigating the impact of modulating caspase-8 activity on apoptosis.
  • Assessing the effects of targeting caspase-8 pathways on drug-resistant malignancies.

Main Results:

  • Altered caspase-8 expression or its inhibition (e.g., by FLIP or Bcl-2) can lead to tumor resistance to cytotoxic drugs.
  • Mechanisms of resistance include decreased caspase-8 expression, increased caspase-8 inhibitors, or sequestration by Bcl-2.
  • Modulating caspase-8 activity presents a potential strategy to enhance cancer cell apoptosis.

Conclusions:

  • Caspase-8 plays a crucial role in mediating the toxicity of chemotherapeutic agents.
  • Understanding resistance mechanisms involving caspase-8 is vital for effective cancer therapy.
  • Targeting caspase-8 and apoptosis pathways offers a promising approach to sensitize drug-resistant cancers to treatments like radiation and chemotherapy.

More Related Videos

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...