Related Experiment Video

Updated: Oct 3, 2025

Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations
08:21

Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations

Published on: July 21, 2023

1.5K

Nitric oxide in multikinase inhibitor-induced hand-foot skin reaction

Leying Chen1, Zhaoyu Wu1, Linan Yang1

  • 1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Translational Research : the Journal of Laboratory and Clinical Medicine
|February 21, 2022
PubMed

Insights

Glyceryl trinitrate (GTN), a nitric oxide donor, effectively treats hand-foot skin reaction (HFSR) caused by multikinase inhibitors (MKIs). This study shows GTN mitigates HFSR symptoms and improves patient quality of life without compromising anti-cancer effects.

Area of Science:

  • Oncology
  • Dermatology
  • Pharmacology

Background:

  • Hand-foot skin reaction (HFSR) is a common, debilitating side effect of multikinase inhibitors (MKIs) targeting vascular endothelial growth factor receptor (VEGFR).
  • Current treatments for HFSR are lacking, and its precise pathogenic mechanisms remain unclear, impacting cancer therapy continuation and patient quality of life.
  • Nitric oxide (NO) signaling pathways are implicated in cellular processes affected by VEGFR inhibition.

Purpose of the Study:

  • To investigate the therapeutic potential of nitric oxide, specifically glyceryl trinitrate (GTN), in mitigating MKI-induced HFSR.
  • To elucidate the underlying mechanisms by which NO may counteract VEGFR inhibition-related toxicities.
  • To evaluate the efficacy and safety of topical GTN in preclinical models and human patients with HFSR.

Main Methods:

  • In vitro studies using cell cultures to assess GTN's effects on proliferation, migration, and apoptosis induced by MKIs.
  • Preclinical testing in a rat model to evaluate GTN's impact on tissue damage.
  • In vivo efficacy study in HepG2 tumor-bearing mice to assess GTN's effect on MKI anti-tumor activity.
  • Clinical trial involving HFSR patients treated with GTN ointment.

Main Results:

  • In vitro, GTN demonstrated protective effects against MKI-induced cellular toxicity, promoting cell proliferation and migration while reducing apoptosis.
  • Local GTN application in rats significantly mitigated tissue damage associated with MKI treatment.
  • In mice, GTN did not interfere with the anti-tumor efficacy of MKIs.
  • Topical GTN treatment in HFSR patients led to alleviation of cutaneous symptoms and improved quality of life.

Conclusions:

  • Nitric oxide, delivered via glyceryl trinitrate, represents a promising therapeutic strategy for managing MKI-induced hand-foot skin reaction.
  • GTN counteracts VEGFR inhibition toxicity by upregulating downstream signaling pathways, offering a novel mechanism for HFSR treatment.
  • The findings support GTN as a potential adjunct therapy to improve the tolerability and therapeutic window of MKI-based cancer treatments.

More Related Videos

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds08:23

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Published on: February 16, 2022

4.3K
En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries08:58

En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries

Published on: February 25, 2016

9.7K

Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.2K
Antihypertensive Drugs: Vasodilators01:23

Antihypertensive Drugs: Vasodilators

Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
689
Antianginal Drugs: Nitrates and β-Blockers01:16

Antianginal Drugs: Nitrates and β-Blockers

In cardiovascular health, antianginal drugs combat angina pectoris — a condition marked by chest pain owing to diminished blood flow to the heart.
Organic nitrates,  such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
812
Allergic Drug Reactions01:27

Allergic Drug Reactions

Allergic reactions related to drugs are hypersensitivity responses driven by the immune system and bear no connection to the drug's therapeutic action. While drugs in isolation do not trigger an immune response, they can interact with endogenous proteins to form antigens. These antigens stimulate lymphocytes to produce antibodies. IgE-type antibodies attach themselves to mast cells. Upon subsequent exposure to the same stimulus, the antigen-antibody interaction is initiated, unleashing...
1.0K