We have shown that the quadruplex-forming oligonucleotide,AS 1411 (Antisoma),selectively inhibits cancer cell proliferation and has significant clinical activity in a Phase Ⅰ clinical trial with no toxicity.Its growth inhibitory activity correlates with its ability to bind the ubiquitous cellular protein,nucleolin.We have also demonstrated that naturally occurring genomic quadruplex-forming sequences are also selectively growth inhibitory for transformed cells.These sequences occur in eukaryotic telomeres as well as in the promoters of growth regulatory genes,including c-myc where quadruplex-formation appears to play an important role in regulating c-myc expression.The c-myc quadruplex-forming sequence (Pu27) occurs upstream of the c-myc P1 and P2 promoters which are responsible for more than 95% of total c-myc expression.