As oncology research evolves, the scientists have discovered that the cancer stem cells, which can be found in many types of cancer, are responsible for the metastatic cancer and its recurrence. However, there are still many major questions unanswered, such as what are the characteristics of cancer stem cells, how they cause diseases, why they develop drug resistance, what are their drug resistance mechanisms and many others. To solve those questions, scientific researchers have been attempting to research cancer stem cells individually so that they can develop a clearer, more in-depth and accurate understanding of it.

Days ago, researchers from Nankai University, Southern Medical University, Tianjin Medical University and Yale University published a research in the interdisciplinary premium open access journal Advanced Science. Using single-cell RNA sequencing combined with telomere length analysis, they identified the different states and molecular characteristics of colorectal cancer stem cells. Cancer stem cells with strong stemness actually take up a low portion with a low proliferation rate They are usually in a resting state and keep their telomeres short. These silent killers not only evade current tumor therapies that prevent cell proliferation and induce apoptosis, but also develop drug resistance through dormancy, and can mutate and remodel into proliferating tumor epithelial cells, thus leading to rapid growth of cancer cells and cancer recurrence. This finding has altered our understanding of cancer stem cells and provided a new idea for cancer treatments, especially for reducing the risk of cancer recurrence.

The figure shows the researchers using single-cell RNA sequencing combined with telomere length analysis, finding out that colorectal cancer stem cells exist in different states.

Colorectal cancer is the third most common occurring cancer. It is also the number three killer in terms of mortality rate and nowadays it shows a likeability to appear in younger people. Studies found out that cancer metastasis and recurrence are the main causes of death for most patients with terminal colorectal cancer. Nowadays, the commonly used treatment, which mainly target cancer cells in a proliferative state, can significantly improve early treatment outcomes, but patients often develop drug-resistant responses that lead to recurrence and metastasis. Further studies also revealed that cancer stem cells are an inducing factor that results in the recurrence of colorectal cancer after the treatment.

This findings suggest that cancer metastasis and recurrence are closely associated with resting cancer stem cells. Although conventional cancer treatment can kill proliferating cancer cells well, resting cancer stem cells are likely to develop drug resistance. Similarly, telomerase inhibitory drugs can only work on proliferating telomerase positive cancer cells, but not the targeted therapies against resting cancer stem cells with short telomeres and low telomerase activity. These findings will offer useful references for optimizing cancer treatment that effectively target against cancer stem cells and alleviate drug resistance.

Prof. Liu Lin from Nankai University, Prof. Pan Xinghua from Southern Medical University, Prof. Qi Feng from Tianjin Medical University, and Prof. Sherman M. Weissman from Yale University are the corresponding authors of this published research. Wang Hua and Gong Peng, graduated PhD students from College of Life Sciences of Nankai University, are co-first authors. The research was supported by the international cooperation program of the Ministry of Science and Technology.

Click the links below to read the thesis：

https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202004320

(Reported by Junhui Wu, Translated by Meixu Wu, Edited by Davide Francolino and JianjingYun)