2015 Antineoplastics

DIFFERENTIATING AGENTS

One hallmark of malignant transformation is differentiation block.  Numerous chemicals --- including vitamin D and its analogues, retinoids (vitamin A derivatives such as TRETINOIN), rexinoids (multifunctional nuclear retinoid X receptor ligands such as BEXAROTENE), inhibitors of histone deacetylase (HDAC) and DNA methylation --- can all induce tumour cell differentiation, ultimately leading to apoptosis.
Critical fact icon
  • differentiation block is characteristic of several leukemias

  • an example of this occurs due to the t(15;17) translocation in acute promyelocytic leukemia (APL)
    • this translocation creates a fusion protein (PML-RAR α) consisting of portions of the retinoic acid receptor and promyelocytic leukemia protein
    • in the absence of an agent to stimulate the receptor, the fusion protein binds to DNA and prevents activation of genes required for differentiation

  • two of the drugs in this class (TRETINOIN, ARSENIC TRIOXIDE) are approved for APL, and are under investigation for use in other diseases with a similar profile (as are many other drugs)
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 10-may-15 9:07 PM