Pharmacogenetic considerations for non-Hodgkin's lymphoma therapy.
BACKGROUND
Chemotherapy is the current standard treatment for hematological malignancies for both curative and palliative purposes. Unfortunately, in the current treatment scenario chemotherapy resistance is an issue that is know to lead to a relapse in cancer. The multidrug resistance 1 (MDR1) gene is often involved in drug resistance and, so far, the best studied mechanism of resistance relates to the level of P-glycoprotein (P-gp) expression on cancer cells; however, correlation with single nucleotide polymorphism (SNP) in the MDR1 gene has also been observed via a number of different mechanisms that interfere with function and expression of P-gp.


METHODS
This article describes the influence of P-gp expression and SNP on the MDR1 gene in non-Hodgkin's lymphoma (NHL) and their effect on both its risk and outcome. The authors also provide a brief summary of the more important therapeutic options, which aim to overcome this drug resistance mechanism, and discuss their known mechanisms of action.


CONCLUSIONS
There is evidence pertaining to an association between the outcome of NHL and P-gp expression. However, the authors emphasize the need for more studies to reinforce this evidence. Furthermore, there is a definite need for the therapeutic targets, which provide tumor cellular lines of interest, to be tested in humans, in order to better evaluate their toxicity and overall effect on the outcome. The ultimate aim of this research is to develop specifically designed therapies that are tailored to the intrinsic characteristics of specific patients.
Servico de OncoHematologia, Portuguese Institute of Oncology , Porto , Portugal.
Ana
A
Espirito Santo
Rui
R
Medeiros
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1