Newly-reported research involves progress in disabling cancer stem cells via the notch pathway. Regarding cancer stem cells, see the blog entry Big pharma is targeting cancer stem cells. “As I wrote in my July 2009 post On cancer stem cells, most cancer therapies are based on killing cancer cells – as many cells as possible. But cancers frequently and persistently recur after bouts of radiation or chemotherapy. The culprit is thought to be cancer stem cells, where any surviving ones simply go about making new cancer cells. A new therapeutic concept is therefore to focus on killing the cancer stem cells. “While normal stem cells are essential for development, play a key role in tissue maintenance, and aid in repair, cancer stem cells are believed responsible for tumorigenesis, metastases, and cancer recurrence(ref).” I reported further research regarding cancer stem cells in my August 2009 blog post Update on cancer stem cells.”
I also briefly discussed how the Notch pathway is involved in tumorgenesis in the blog post Niche, Notch and Nudge.
A news report appeared yesterday indicating “Studies in animals and women with advanced breast cancer showed the experimental compound MK-0752, under development by Merck & Co Inc, was able to kill off cancer stem cells that linger in the breast after chemotherapy. — In the latest study, supported by funding from Merck, Chang and colleagues injected mice with breast cancer cells taken from patients and grew human tumors in the mice that were identical to those growing in women. The team then studied the specific properties of the cancer stem cells, and focused on the Notch pathway, which is important for normal development of breast tissue. “We found this was also active in cancer stem cells,” Chang said in a telephone interview. Chang said breast cancer stem cells were dependent on the Notch pathway for survival. Merck’s drug MK-0752, a compound called a gamma-secretase inhibitor, blocks that pathway. When the team combined the drug with regular chemotherapy in mice, “we found we managed to hit cancer stem cells,” Chang said.”
The team also did a small human study involving 35 women with advanced breast cancer. Breast cancer biopsies before and after treatment show the MK-0752 treatment reduces the number of breast cancer stem cells. “In the human studies, the researchers evaluated the stem cells or tumor initiating cells in biopsies taken before and after treatment. In both human and animal studies, inhibition of the pathway reduced the population of these tumor-originating cells that would otherwise remain after chemotherapy. — The next step in research is to take this into larger studies involving patients (Phase III clinical studies), Chang said. “If what we believe is true, we would eventually start using this therapy earlier in treatment,” said Chang(ref).”