colon cancer stem cell treatment. pri 724 to treat colorectal cancer. dr. anton titov, md: you have developed a metastatic colon cancer treatment medication which is in clinical trials now. this colon cancer therapy is called pri-724. it's a very exciting colorectal cancer therapy medication that targets a particular molecular pathway, the wnt and beta-catenin. you worked with dr. michael kahn in the comprehensive cancer center to develop this stage 4 colon cancer treatment medication. can you tell us about this colon cancer medication? what this new colon cancer therapy might bring to the patients in the future? dr. heinz-josef lenz, md (colorectal cancer expert, california): it's very important to know that we cannot cure colon cancer with chemotherapy alone. and why is that? well, i usually use the example of a tree. this analogy helps to understand why our chemotherapy ultimately fails. it helps to understand why we need in patients with stage 4 colorectal cancer liver metastases surgery to cure the patient. and the reason is when we start chemotherapy in stage 4 colorectal cancer patient with liver metastases, the success rates are very high, response rate of 60% to 70%. but if the metastatic stage 4 colon cancer tumor starts growing again and we need to switch chemotherapy, the colon cancer tumor response rate goes down to 10% or 20%. and in third line of metastatic stage 4 colon cancer treatment the response rate falls to 2%. why? are the treatments just weaker? or what happened to the colon cancer tumor? so, i think what's happening is like when you have a tree and you want to cut the tree down. this is the analogy. when we give metastatic stage 4 colon cancer patient chemotherapy, we are able to remove leaves from the tree.
when we surgically remove the metastatic stage 4 colon cancer tumors in the liver, it's like we are cutting branches of the tree. when we remove primary colon cancer tumor, maybe it's like cutting the the stem of the tree. but the tree always grows back, and metastatic stage 4 colon cancer tumor often returns. dr. heinz-josef lenz, md (colorectal cancer expert, california): so, how can we cure colon cancer when we are only able to cut branches the colon cancer "tree" but not unroot the tree? so, how do we unroot the tree? well, the roots of colon cancer and other cancers are the colon cancer stem cells. and cancer stem cells are, by definition, resistant to any chemotherapy treatments we have for colon cancer patient. so, how can we target cancer stem cells? well, we cannot kill cancer stem cells. we can only stimulate cancer stem cells, so they differentiate out. and then we can kill differentiated cancer stem cells with chemotherapy. so we developed and we used pri-724 medication candidate for the first time in the clinic. we were able to show that we can eliminate colon cancer stem cells in pre-clinical colon cancer models. our success led to the first in human, proof of principal, clinical trial. and actually we monitored the efficacy of pri 724 by using circulating colon cancer tumor cells. dr. heinz-josef lenz, md (colorectal cancer expert, california): we knew if the pri-724 worked, what happens to pri-724 molecules in the body, we monitored the cancer stem cell markers. so, i think for the future, we need colon cancer medications which target the underlying roots of the colon cancer. these new medications will first differentiate colon cancer stem cells out. then we can kill colon cancer stem cells with chemotherapy. so, i think that is how we will be able, in the future, cure stage 4 colon cancer. we will cure colon cancer when we find the right drugs which can actually differentiate cancer stem cells and kill them.
now, we know that from other cancers that retinoic acid differentiates out leukemia cells. then you can kill them and you can cure the cancer patient. probably it's not as simple in colon cancer and other cancers, but i think that is the right approach to treat metastatic stage 4 colon cancer. pri-724 was one of the first drugs to to target wnt signaling. now, wnt gene is altered in over 95% of colon cancer tumors. wnt is an extremely interesting pathway. because wnt is the first pathway which is activated in a developing life. so when you have four cells, the pathway which activates first is wnt because at this point you already need to know that you have to grow. but you already need to know what cells will develop into legs, into organs. cells of growing human body need to know their directions. so, it's a process of differentiation and proliferation. and that has been the challenge in the past. you cannot just inhibit wnt pathway altogether. inhibiting both proliferation and differentiation would be too toxic. dr. heinz-josef lenz, md (colorectal cancer expert, california): you need to inhibit the proliferation part of wnt pathway. and you need to stimulate the differentiation part, of wnt pathway. then you have a chance of cure for colon cancer. so, i think that wnt is a key pathway in the future to develop new colon cancer treatment medications against it. and that's the way we can cure stage 4 metastatic colon cancer in the future.
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