Understanding Mechanisms of Targeted Antineoplastic Therapies, Conclusion: Antineoplastic Therapies

Understanding Mechanisms of Targeted Antineoplastic Therapies, Introduction

Understanding Mechanisms of Targeted Antineoplastic Therapies, Mechanism of Action

Bexarotene: Results

• Exposure is directly correlated with the expression of several genes that play important roles in:
  • Cellular differentiation
  • Proliferation
  • Apoptosis
• Bexarotene is expanding the frontiers of treatment with oral small molecules that target intracellular pathways

Oral chemotherapeutics 

• Small molecules target malignant cells becoming treatments of choice for neoplastic diseases

Tyrosine Kinase Inhibitors

• Activated after an extracellular ligand binds to the kinase associated receptor

Selective inhibition

• Disrupt intracellular signaling events 
• Eventually impact cellular homeostasis and regulation of gene expression

Nuclear hormone receptor modulators

• Play a direct role in regulating gene expression
• Bexarotene, agonist for the Retinoid X Receptors

RXR

• Binds in pairs with other nuclear receptors to specific sequences on the DNA 
• Governs gene expression

Bexarotene

• High affinity to ligand binding domain of the RXR's
• When binding to the Retinoid X Receptor, it causes conformational changes to the receptor-ligand complex