USING APOPTOSIS TO TREAT CANCER
Scientists have been trying to induce death in cancer cells for many years, usually with radiation or chemotherapy. The drawback to most current therapies is that they are nonspecific. They kill noncancerous cells as well as cancer cells. However, every mammalian cell contains the genetic information to undergo apoptosis—even cancer cells, although they have overridden the normal controls. Recently, scientists have focused on deliberately inducing apoptosis in cancer cells.
One strategy is to induce the mitochondrial apoptotic pathway. A high level of Bcl-2 protects cells from apoptosis. So if the amount of Bcl-2 were reduced in cancer cells, perhaps they would become more sensitive to apoptosis. (Mice with the Bcl-2 gene deleted die from too much apoptosis, particularly in the lymphoid tissue, where immune B cells mature.) The synthesis of Bcl-2 protein can be reduced by using a single-stranded antisense DNA of 18 nucleotides. Its sequence is complementary to the translation start site of the Bcl-2gene. When the antisense DNA oligonucleotide binds to the Bcl-2 mRNA, translation is blocked, and less protein is made ( Fig. 20.24 ). In a recent clinical trial of patients with B-cell lymphomas, six of 14 patients had a much lower level of Bcl-2 and showed improved anticancer responses.
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