Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases

Abstract Resistance to chemotherapy agents is the main reason for treatment failure in patients with cancer. Multidrug resistance (MDR) is the primary mechanism that leads to the acquisition of the multiresistant phenotype through the overexpression of drug efflux transporters such as the P-glycopro...

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Bibliographic Details
Published in:Cancer letters 2010-09, Vol.295 (2), p.135-143
Main Authors: Pérez-Sayáns, Mario, Somoza-Martín, José Manuel, Barros-Angueira, Francisco, Diz, Pilar Gayoso, Rey, José Manuel Gándara, García-García, Abel
Format: Article
Language:English
Subjects:
Adrenal glands
ATP Binding Cassette Transporter, Sub-Family B
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - physiology
Breast cancer
Cancer therapies
Carcinogens
Carcinoma, Squamous Cell - drug therapy
Cytotoxicity
Drug dosages
Drug resistance
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Genotype & phenotype
Hematology, Oncology and Palliative Medicine
Humans
MDR
Mouth Neoplasms - drug therapy
Multidrug resistance
Oral cancer
Oral squamous cell carcinoma
P-glycoprotein
Radiation therapy
Rodents
Studies
Tumors
V-ATPase
Vacuolar Proton-Translocating ATPases - physiology
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Summary:Abstract Resistance to chemotherapy agents is the main reason for treatment failure in patients with cancer. Multidrug resistance (MDR) is the primary mechanism that leads to the acquisition of the multiresistant phenotype through the overexpression of drug efflux transporters such as the P-glycoprotein (Pgp), encoded by the MDR1 gene, at the plasma membrane. Other molecules that have been implicated in drug resistance include multidrug resistance-associated proteins, glutathione S-transferase-π, and DNA topoisomerase II. These molecules, however, cannot fully explain MDR in oral squamous cell carcinoma. Vacuolar ATPase (V-ATPase), which is largely responsible for regulating acidity in the microenvironment of solid tumors (and hence interfering with the absorption of chemotherapy drugs), seems to be the most important molecule involved in MDR in such tumors. Specific V-ATPase inhibitors, thus, may be useful, not only as coadjuvants in antitumor treatments but also as a mechanism for controlling resistance to antitumor drugs.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2010.03.019