Targeted therapy for malignant melanoma.
Malignant melanoma is a tumor that offers unique possibilities for approaches to targeted therapy by virtue of the pigment biosynthesis pathway. Such approaches may seek to use the incorporation of toxic intermediates or to use the natural transcriptional control of genes coding for enzymes involved in melanin formation to regulate gene therapy. In this paper, we describe how the 5'-flanking sequences of the genes for tyrosinase or tyrosinase-related protein 1 can be used to drive expression of complementary DNA, coding for immunity-stimulating proteins or for drug-activating enzymes, specifically in melanoma cells. The combination of the tissue specificity resulting from these techniques, coupled with innovative delivery systems, should provide the maximum available therapeutic index and lead to the design of new treatments with limited side effects.
Richard Dimbleby Department of Cancer Research, St. Thomas' Hospital, London, UK.
I R
IR
Hart
R G
RG
Vile
D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008545:Melanoma / Q000628:therapy*; D011355:Prodrugs / Q000378:metabolism
D008543:Melanins; D011355:Prodrugs