The expression of some proto-oncogenes (c-myc, N-myc, epidermal growth factor receptor) is frequently enhanced in several human malignant tissues. The reduction of level of this expression through the use of anti-sense RNA or anti-sense oligodeoxynucleotides might therefore offer a new way to modify at the somatic level some genetic traits controlled by these oncogenes and possibly related to the maintenance of the transformed phenotype. This approach, although interesting, is paved with considerable conceptual and technical difficulties: multigene involvement in many natural oncogenic processes as well as delivery and stability of the anti-sense nucleic acids. This paper briefly discusses some of these points and presents preliminary results obtained with the alpha-anomeric oligodeoxyribonucleotides.