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
FAQs
On-target refers to exaggerated and adverse pharmacologic effects at the target of interest in the test system. Off-target refers to adverse effects as a result of modulation of other targets; these may be related biologically or totally unrelated to the target of interest.
What is an on-target adverse drug response? ›
Drugs are intended to interact with specific receptors (intended receptors) in specific tissues (intended tissues). An “on-target” ADR occurs when a drug interacts with its intended receptor in the intended tissue.
What is an off-target side effect? ›
Sometimes a drug used to treat a particular condition or symptom can have effects on other pathways or tissues within the body in addition to the intended target. These are termed as off-target effects and can lead to side effects ranging in severity from mild to life threatening.
What are off-target effects in drug development? ›
Describes the effects that can occur when a drug binds to targets (proteins or other molecules in the body) other than those for which the drug was meant to bind. This can lead to unexpected side effects that may be harmful. Learning about the off-target effects of drugs may help in drug development.
What is the meaning of on and off-target? ›
Off-target activity is biological activity of a drug that is different from and not at that of its intended biological target. It most commonly contributes to side effects. However, in some cases, off-target activity can be taken advantage of for therapeutic purposes.
How do you identify off-target effects? ›
Genome-wide NGS to determine off-target editing
Therefore, before you can properly assess off-target edits, you must first identify potential sites of off-target effects. This is often called “nominating hotspots” and can be done effectively using unbiased techniques such as WGS.
What can off-target effects cause? ›
If these complexes do not bind at the target, often a result of hom*ologous sequences and/or mismatch tolerance, they will cleave off-target DSB and cause non-specific genetic modifications. Specifically, off-target effects consist of unintended point mutations, deletions, insertions inversions, and translocations.
What is off-target toxicity in chemotherapy? ›
Chemotherapy has benefits, but the side-effects can be traumatic. These arise because of what we pharmacologists call “off-target toxicity”, where drugs attack healthy cells as well as disease cells.
What is considered a side effect? ›
An effect of a drug or other type of treatment that is in addition to or beyond its desired effect. Side effects can be harmful or beneficial, and most go away on their own over time.
What is the on off effect in pharmacology? ›
The “on–off” phenomenon refers to the rapid change in motor state from normal to parkinsonian, then back to normal again, sometimes with dyskinesias paralleling blood levels of dopaminergic medications.
A drug target is a specific molecule, often a protein, in the body that is closely linked to a particular disease process and can be influenced by a drug to produce a desired therapeutic outcome.
What is off-target toxicity of chemotherapy? ›
Chemotherapy has benefits, but the side-effects can be traumatic. These arise because of what we pharmacologists call “off-target toxicity”, where drugs attack healthy cells as well as disease cells.
What is an example of shot on target? ›
However, if a shot hits the woodwork and then goes in as a goal, this will count as a shot on target. For example, James Rodriguez's volley for Colombia against Uruguay at the 2014 World Cup was a shot on target, but Frank Lampard's strike against Germany at the 2010 World Cup wasn't, as it didn't count as a goal.
