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 apoptosis, due to overexpression of anti-apoptotic proteins, is involved in tumorigenesis and treatment resistance. Antisense oligonucleotides can be used to specifically inhibit unwanted gene expression and hence target the molecular basis of genetic diseases. Recently developed antisense oligonucleotides with the ability to inhibit the expression of anti-apoptotic proteins, including Bcl-2, Bcl-xL, FLIP and surviving, have been shown to facilitate tumor cell apoptosis and sensitize tumor cells to cytotoxic treatments. This suggests their use in combination with conventional treatments as an approach to more effective cancer therapy.