Targeting tumor cell resistance to apoptosis induction with antisense oligonucleotides: progress and therapeutic potential

Despite the use of combination chemotherapy and immunotherapy, the survival rate of adult cancer patients has only moderately increased. Diminished ap optosis, due to overexpression of anti-apoptotic proteins, is involved in t umorigenesis and treatment resistance. Antisense oligonucleotides can be us ed to specifically inhibit unwanted gene expression and hence target the mo lecular basis of genetic diseases. Recently developed antisense oligonucleo tides with the ability to inhibit the expression of anti-apoptotic proteins , including Bcl-2, Bcl-xL, FLIP and survivin, have been shown to facilitate tumor cell apoptosis and sensitize tumor cells to cytotoxic treatments. Th is suggests their use in combination with conventional treatments as an app roach to more effective cancer therapy. (C) 2001 Harcourt Publishers Ltd.