On-Target and Off-Target Side Effects

Grace Dy, MD, Associate Professor, Department of Medicine, Roswell Park Cancer Institute, gives an overview of on-target and off-target side effects from anticancer targeted agents.

Grace Dy, MD, Associate Professor, Department of Medicine, Roswell Park Cancer Institute, gives an overview of on-target and off-target side effects from anticancer targeted agents.

On-target side effects refer to the pharmacodynamic effect on normal tissues that occurs when the target that's being inhibited in the tumor is also being inhibited in the normal tissue. Common on-target side effects include skin rash from inhibitors of the MAP kinase pathway or ocular toxicities from MEK inhibitors, Hsp90 inhibitors, and selective FGFR inhibitors.

Clinical Pearls

Off-target side effects are unexpected and are due to the effects from other targets or the structure of the drug.

  • On-target side effects refer to the pharmacodynamic effect on normal tissues
  • Off-target side effects are unexpected and are due to the effects from other targets or the drug's structure