Cancer stem cells hold keys for cure of colorectal cancer. How cancer stem cells can be found and killed by new cancer treatments? How to use immunotherapy to cure colorectal cancer in carefully chosen patients?

Colon cancer stem cells or tumor-initiating cells are the reason for systemic chemotherapy failure in colon cancer treatment. Dr. Anton Titov, MD. You have a very large experience in advancing stem cell technologies for treatment of colorectal cancer. Dr. Anton Titov, MD. What is the role of cancer stem cells in colorectal cancer? What advances in stem cell technologies can help colorectal cancer treatments? Prof. Dr. Hans-Joachim Schmoll, MD. The key to any cancer is the cancer stem cell. Cancer stem cell is exactly the cell this was strong enough to overcome the immune system. Cancer stem cells can overpower local resistance mechanisms to the developing tumor cells. that tumor can develop. At any time in our body we develop cancer cells. But the vast majority of the cancer cells are killed. Cancer cells die on their own. Or immune cells kill most developing cancer cells. But there are few cancer cells this escape body defense at some time point. Prof. Dr. Hans-Joachim Schmoll, MD. This cancer cell escape is possible because cancer stem cells are strong enough and deviant enough from the normal tissue cells. Cancer cells have a growth advantage over normal cells. Cancer cells must be killed at the right time. Cancer stem cells can really grow fast. Cancer stem cells divide. They can easily develop into less malignant clones. But also cancer stem cells can develop more malignant clones in time. Dr. Anton Titov, MD. Then they can also develop other cancer stem cells. Some of new cancer stem cells are even more malignant than the primary stem cell. We detect colon cancer tumor by colonoscopy, for example, or by CT or MRI or PET during metastatic cancer investigation. Prof. Dr. Hans-Joachim Schmoll, MD. Clinically detected cancer has a collection of different cancer stem cells, this are derived from the initial cancer stem cell. The problem is this. Cancer stem cells are usually more resistant to any chemotherapy. Dr. Anton Titov, MD. Cancer stem cell is also resistant to immunotherapy in comparison to its daughter cells. For example, you can give chemotherapy to a tumor like colon cancer with metastases in the liver. The patient is lucky and the treatment works very well. Then we can probably eliminate 90% of the tumor cells in the liver and in the body by the chemotherapy. But that 10% of residual cancer contains cancer stem cells. We can resect remaining 10% of tumor by surgery. But this is a macroscopic treatment of tumor. Surgery is not a microscopic management. Prof. Dr. Hans-Joachim Schmoll, MD. This is a problem. Microscopic stem cells reside in remaining tumor. They can develop new metastases at the same place. Or they also migrate to other organs and do further metastasis. this is the key to cancer treatment. How to kill the cancer stem cell? Even if it is possible to kill most of the "daughter cells" of colon cancer tumor. It is not clear now how to kill cancer stem cells. What is the best molecular key to find and kill cancer stem cells? There are many antibodies developed. But the problem is cancer stem cells are variable. Cancer stem cells evolve. Prof. Dr. Hans-Joachim Schmoll, MD. It is not so easy to find one molecule that will kill all cancer stem cells. Someday we will kill cancer stem cells. But for now a lot of research is necessary to fight cancer stem cells. There is another option to kill cancer stem cells. It is probably more helpful and very recent method. It is immunotherapy. Immunotherapy is surprisingly active in other tumors. In kidney cancer or melanoma. This is real immunotherapy. It means we let immune cells attack the tumor cells. Even when body's own immune system was not working normally. Otherwise a tumor would not grow. Prof. Dr. Hans-Joachim Schmoll, MD. T-cell checkpoint inhibitors can activate immune T-cells. Such toxic T-cells can kill the tumor. Immunotherapy works in many tumor types. It is very good last-line treatment. Now it is going to first-line therapy. But in colorectal cancer immunotherapy doesn't work very well at the moment. We think the key is to select a specific subgroup of colon cancer patients. It is 5 to 10% of patients. It is important to let the immune cells do their work in the tumor cells and colon cancer stem cells. I'm sure in few years the research will show how to use immunotherapy to kill colon cancer stem cells. Prof. Dr. Hans-Joachim Schmoll, MD. But this is the optimal means to eliminate the tumor cells. Just by the activated normal human immune cells. it is also a question of selecting the right patients for immunotherapy. Dr. Anton Titov, MD. Those 5% - 10% of colon cancer patients. Immunotherapy might work for them even at the present level of technology. There is specific group of colon cancer patients for whom immunotherapy may work. These tumors have MSI characteristic. MSI is MicroSatellite Instability. MSI colon cancers have a particularly high mutation rate in the tumor. Dr. Anton Titov, MD. High mutation rate inside tumor attracts many immune T-cells into the tumor. T-cells are activated by immune checkpoint inhibitor medications. Checkpoint inhibitors are antibodies for colorectal cancer treatment. Immune checkpoint inhibitors are very active in MSI-positive colorectal cancer. But these are only 5% to 15% of all colon cancers. It depends on the patient population. for the majority of colon cancer patients immune checkpoint inhibitors have no efficacy. Prof. Dr. Hans-Joachim Schmoll, MD. We need to do more research on immunotherapy for colon cancer. We hope that immunotherapy research will bring results for patients in the near future. Thank you. [Immune checkpoint inhibitors: Keytruda , Yervoy , Opdivo , Ofatumumab Arzerra, Rituximab, Rituxan, Mabthera]. Leading colorectal cancer oncologist and research expert discusses colon cancer diagnosis and treatment options. Colorectal cancer stem cells and colon cancer immunotherapy. Understanding the colon cancer stem cells holds key to successful treatment of metastatic colorectal cancer. Stem Cells in Colon Cancer are important to find and destroy by chemotherapy. Personalized chemotherapy medications Target Cancer Stem Cells in Colorectal Cancer. Stem cell research in colon cancer is rapidly advancing. Soon we will be able to use stem cell colon cancer treatment for each patient with colorectal cancer. Immunotherapy targets colon cancer stem cells to prevent distant metastases. After initial chemotherapy and tumor resection Microscopic stem cells reside in remaining tumor. How to kill the cancer stem cell? Immunotherapy is surprisingly active in kidney cancer or melanoma. But not in colorectal cancer. How active is immunotherapy in colon cancer? How to select the right patients for immunotherapy.