Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases.
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-pi, 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.
Pérez-Sayáns
Mario
M
Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Santiago de Compostela CP, Spain. perezsayans@gmail.com
Somoza-Martín
José Manuel
JM
Barros-Angueira
Francisco
F
Diz
Pilar Gayoso
PG
Rey
José Manuel Gándara
JM
García-García
Abel
A
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy*; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D025262:Vacuolar Proton-Translocating ATPases