Targeted Therapy

Overview

Hydroxyurea

• Mechanism 
  • inhibits ribonucleotide reductase
  • leads to decreased DNA synthesis
    • S-phase specific
• Clinical use
  • melanoma
  • CML
  • sickle cell disease
    • via increased HbF
• Toxicity
  • myelosuppression
• GI upset

Trastuzumab (Herceptin)

• Mechanism
  • anti-HER-2 (erb-B2) monoclonal antibody
• Clinical use
  • HER-2 positive breast cancer
• Toxicity
• cardiotoxicity

Tamoxifen, raloxifene

• Mechanism
  • selective estrogen receptor modulator (SERM)
  • estrogen antagonist in estrogen receptor-positive breast cancer cells
  • estrogen agonist in other tissues
    • bone
• Clinical use
  • breast cancer
  • prevent osteoporosis
• Toxicity
  • ↑ risk of endometrial carcinoma
    • tamoxifen only
      • via partial agonist effects
    • raloxifene is endometrial antagonist
• hot flashes

Imatinib (Gleevec)

• Mechanism
  • Philadelphia chromosome bcr-abl tyrosine kinase inhibitor 
    • t(9;22) translocation
• Clinical use
  • CML
  • GI stromal tumors
• Toxicity
• fluid retention

Rituximab

• Mechanism  
  • anti-CD20 monoclonal antibody
    • most B cell neoplasms are CD20 positive
• Clinical use
  • non-Hodgkin’s lymphoma
  • chronic lymphocytic leukemia
  • rheumatoid arthritis
    • with methotrexate