Prostate cancer therapy – study suggests new molecular screening theory

Smad7 protein levels may predict therapy response

Levels of the Smad7 protein may predict therapeutic response in patients with prostate cancer according to research published today by investigators at the Uppsala Branch of the Ludwig Institute for Cancer Research (LICR).

“Although the 2-ME compound is in early clinical trials, no-one has fully understood the molecular mechanisms of how it causes the death of cancer cells, but not normal cells,” says Dr. Maréne Landström, the senior author of the paper published in the prestigious Journal of Biological Chemistry. “We found that 2-ME works through a protein called Smad7, and that artificially lowering the amount of Smad7 in prostate cancer cells reduced 2-ME’s ability to cause cell death. This finding suggests that the levels of Smad7, and other proteins in this molecular pathway, might predict the cell-killing ability of other cancer therapeutics and thus their effectiveness for treating individual patients.”

Smad7 was originally discovered at the LICR Uppsala Branch in 1997, and the team reported, in the journal Nature, that the protein stopped cell growth by inhibiting a crucial oncogene known as TGF beta. As a result of the current study, Smad7 is now thought to play a crucial role connecting the mechanisms of cell growth, governed by TGF beta, and those of cell death, governed by another oncogene, p38 MAPK.

Dr. Carl-Henrik Heldin, Director of both the Uppsala Branch and LICR’s international ’TGF beta Program’ cautions that the research is at a preliminary stage and that more work is now needed to investigate whether the levels of Smad7 correlate with patients’ responses to different therapies. “If we can determine which patients are most likely to benefit from a particular therapeutic approach, we can reduce the possibility that a patient will undergo treatment that has side-effects but no benefit. More importantly, we may one day be able to effectively target each individual patient with the therapy-type best for him.”