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Targeting cancer stem cells for cancer therapy
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Abstract:
Cancer stem cell (CSC) is characterized by unique molecular expression, surface markers, stemness-related signaling pathways, and metabolic patterns. CSC has been the key factor for the growth, metastasis and treatment resistance in various malignancies, as well as the important reason for the tumorigenesis and recurrence due to its high tumorigenicity, metastatic potential and resistance. Normal stem cells can develop gradually into pre-cancerous stem cell (pCSC) and CSC after incurring the first oncogenic mutation. Subsequently, under the co-influence of oncogenic mutations and tumor microenvironments, oncogenic mutations are accumulated in cells, which further aiding up to tumor heterogeneity, and eventually, promote the tumorigenesis, development, relapse, metastasis, and resistance in combination with CSC plasticity transformation. In order to improve clinical outcome in tumor treatment, various therapeutic strategies targeting CSC have been developed, including cell surface markers, signal pathways, microenvironment, and metabolic patterns. Other strategies such as the promotion of CSC differentiation and immunotherapy targeting CSC are also studied. In clinical trials, several new anti-cancer drugs targeting CSC have shown favorable outcomes in patients. However, the failed attempt of some new anti-cancer drugs also holds noteworthy lessons for future development. Therefore, the specific targeting of all heterogeneous CSCs in tumor of patients and the simultaneous elimination of pCSC and progeny tumor cells will be conducive to inhibitting tumor growth, metastasis and recurrence, expecting to bring new hope for tumor therapy.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 82073278), the Medical and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences (No.2016-I2M-3-013), and the Independent Issue of State Key Laboratory of Molecular Oncology (No.SKLMO-2021-17)
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