Related Experiment Videos

The role of apoptosis-related genes in non-small-cell lung cancer

Eelco Fokkema1, Harry J M Groen, Coby Meijer

  • 1Department of Pulmonary Diseases, University Hospital Groningen,The Netherlands.

Clinical Lung Cancer
|January 7, 2004
PubMed

Insights

Drug resistance in non-small-cell lung cancer is a major challenge. Understanding apoptosis pathways and related proteins offers new therapeutic targets to overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Drug resistance is a significant challenge in non-small-cell lung cancer (NSCLC) treatment.
  • Mechanisms of resistance include intrinsic and acquired pathways, with apoptosis defects playing a crucial role.

Purpose of the Study:

  • To explore the role of apoptotic pathways and related proteins in chemoresistance of NSCLC.
  • To identify potential therapeutic targets for overcoming drug resistance.

Main Methods:

  • Review of existing literature on apoptosis, drug resistance, and NSCLC.
  • Focus on key regulators like p53, retinoblastoma gene, and bcl-2 family.
  • Examination of death receptor-mediated and EGFR-downstream apoptotic pathways.

Main Results:

  • Mutations and defects in apoptosis pathways contribute significantly to NSCLC drug resistance.
  • Proteins involved in apoptosis, including tumor suppressor genes and bcl-2 family members, are critical determinants of drug sensitivity.
  • Naturally occurring ligands and drug-induced pathways targeting apoptosis are areas of active research.

Conclusions:

  • Understanding proteins that govern chemoresistance is vital for developing novel NSCLC treatments.
  • Targeting apoptotic pathways presents a promising strategy to enhance therapeutic efficacy and overcome resistance.

Related Concept Videos

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...
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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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.