Related Experiment Video
Updated: Jul 5, 2026
Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
Published on: November 1, 2017
Improving chemotherapeutic drug penetration in melanoma by imatinib mesylate
Youichi Ogawa1, Tatsuyoshi Kawamura, Masao Furuhashi
1Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Background:
Imatinib mesylate has specific activity in inhibiting select tyrosine kinase receptors, including platelet-derived growth factor receptors (PDGFRs) and c-kit. In general, melanomas widely express PDGFR and c-kit, and their in vivo resistance to chemotherapy is attributable to high tumor interstitial fluid pressure (IFP). Recent studies have suggested that PDGFR-beta inhibition reduces tumor IFP, and thus increases the uptake of concomitantly administered drugs.
Objective:
The present study was designed to investigate the potential of imatinib mesylate as a therapy for melanoma or as an adjuvant to chemotherapeutics.
Methods:
Using in vivo mouse models, the effect of imatinib mesylate on the growth of melanoma with or without dacarbazine was studied.
Results:
Imatinib mesylate enhanced the antitumor effect of dacarbazine on in vivo growth and lung metastases of melanoma cells, although treatment with only imatinib mesylate had no effect. We could detect perivascular expression of PDGF beta-receptor in melanoma tumors. Interestingly, dacarbazine uptake in melanoma was more than three-times increased by treatment with imatinib mesylate, while its uptake in serum or bone marrow was not affected by imatinib mesylate.
Conclusions:
These data suggest interference with PDGF receptors, or their ligands, as a novel strategy to increase drug uptake and therapeutic effectiveness of chemotherapy for melanoma.
Insights
Imatinib mesylate enhances dacarbazine chemotherapy for melanoma by increasing drug uptake. This targeted approach improves melanoma treatment effectiveness by inhibiting platelet-derived growth factor receptors (PDGFRs).
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Melanoma often exhibits resistance to chemotherapy due to high tumor interstitial fluid pressure.
- Platelet-derived growth factor receptors (PDGFRs) and c-kit are frequently expressed in melanomas.
- Inhibiting PDGFR-beta has shown potential in reducing tumor interstitial fluid pressure and enhancing drug delivery.
Purpose of the Study:
- To evaluate imatinib mesylate as a melanoma therapy or adjuvant to chemotherapy.
- To investigate the impact of imatinib mesylate on melanoma growth and drug uptake.
Main Methods:
- In vivo mouse models were utilized to study melanoma growth.
- The effects of imatinib mesylate alone and in combination with dacarbazine were assessed.
- Dacarbazine uptake in tumors, serum, and bone marrow was measured.
Main Results:
- Imatinib mesylate significantly enhanced the antitumor effects of dacarbazine against melanoma growth and lung metastases.
- Perivascular expression of PDGF beta-receptor was observed in melanoma tumors.
- Dacarbazine uptake in melanoma was increased over threefold with imatinib mesylate, without affecting uptake in serum or bone marrow.
Conclusions:
- Targeting PDGF receptors or their ligands presents a novel strategy for enhancing chemotherapy drug uptake.
- Imatinib mesylate, by interfering with PDGF signaling, can improve the therapeutic effectiveness of chemotherapy for melanoma.
More Related Videos
Related Concept Videos
01:27Bioavailability Enhancement: Drug Permeability Enhancement
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...