NF-κB as a Potential Target for the Treatment and Prevention of Mucositis

Prathapan Abeesh1, Chandrasekaran Guruvayoorappan1

  • 1Laboratory of Immunopharmacology and Experimental Therapeutics, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, 695011, Kerala, India.

Insights

Nuclear factor-kappa B (NF-κB) is key in chemotherapy and radiation-induced mucositis. Targeting NF-κB offers a promising strategy for managing this severe side effect in cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Mucositis, a severe side effect of cancer therapies, significantly impacts patient quality of life and incurs high healthcare costs.
  • Current treatments for mucositis are limited, necessitating novel therapeutic strategies.
  • Intracellular signaling pathways, particularly nuclear factor-kappa B (NF-κB), are increasingly recognized for their role in mucositis pathogenesis.

Approach:

  • This review synthesizes recent research on the mechanisms of mucositis development.
  • It focuses on elucidating the functional significance and signaling pathways of NF-κB activation in mucositis.
  • The review examines evidence linking NF-κB to mucosal injury and disease progression.

Key Points:

  • NF-κB signaling is a central pathway in the development and progression of mucositis.
  • Altered NF-κB expression correlates with increased mucosal damage in mucositis.
  • Targeting NF-κB activation presents a potential therapeutic avenue for managing mucositis.

Conclusions:

  • NF-κB represents a critical therapeutic target for mitigating chemotherapy and radiotherapy-induced mucositis.
  • Regulating NF-κB activation could offer a powerful strategy for clinical mucositis management.
  • Further research into NF-κB pathways may lead to more effective mucositis treatments.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.6K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
188
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
216
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
166
Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents01:24

Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents

In the intricate landscape of the gastric lumen, excessive acid secretion disrupts the natural defense mechanisms, weakening the mucus-bicarbonate barrier. This vulnerability allows pepsin to infiltrate epithelial cells, digesting mucosal proteins and triggering erosion, leading to ulcer formation.
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
594
Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents01:20

Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents

The gastric mucosa produces prostaglandins E2 (PGE2) and prostacyclin (PGI2), crucial in maintaining gastric health. They exert cytoprotective effects, including increasing bicarbonate secretion, releasing protective mucin, reducing gastric acid output, and preventing harmful vasoconstriction. These effects are mediated through various receptors, such as EP1, EP2, EP3, and EP4.
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
531