The researchers then introduced those sensitive cancer-cell lines into mice, where they grew into tumors. When the lung-tumor-bearing mice were injected with the Smac mimic, the tumors reduced significantly in size, and in some cases, the tumors disappeared completely.
Also tried was a similar experiment treating breast-cancer tumors in mice with the Smac mimic alone. That treatment, however, showed little effect.
The researchers then investigated what made those particular lung-cancer cell lines so sensitive to the Smac mimic alone.
We found that these sensitive cell lines produce their own TNFa, Dr. Wang said.
In addition to aiding in cell death, TNFa also is known, paradoxically, to sometimes play a role in aiding cancer-cell survival and growth. In combination with the Smac mimic, however, the role of this molecule is clear: cell death.
The Smac mimetic is able to exploit certain cancer cells that secrete TNFa and usurp this pro-survival signal to promote cell death, Dr. Wang said.
Not only is single-agent Smac mimetic treatment highly effective at inducing cell death in these cell lines, but it also offers the possibility of highly specific and relatively nontoxic future therapeutic treatments by exploiting certain cancer cells own production of TNFa.
Additional research and tests will be needed before the Smac mimic is tested in humans, Dr. Wang said, adding that detecting the presence of TNFa in a patient could serve as a marker to indicate that the cancer might be sensitive to treatment with the Smac mimic alone.
The challenge for cancer therapies now is that they also tend to kill normally growing cells as well as cancer cells, which results in undesirable side effects, he said. Because this compound affects cancer
|Contact: Amanda Siegfried|
UT Southwestern Medical Center