A Small Molecule Strategy for Targeting Cancer Stem Cells in Hypoxic Microenvironments

2022-04-15 10:42:58
Topic:A Small Molecule Strategy for Targeting Cancer Stem Cells in Hypoxic Microenvironments 
Time:April 19th (Tuesday) at 10 AM
Location:Tencent Conference 187546507
Speaker:Prof. Dr. Jong Seung Kim
Inviter:Prof. Jianliang Shen

Profile:Prof. Dr. Jong Seung Kim, Member of Korea Academy of Science and Technology. 
Current Affiliation:Department of Chemistry (College of Science), Korea University.
Occupation:Professor of Chemistry at Korea University. 
Educational Background:
Aug. 1993 Ph.D (Organic Chemistry), Department of Chemistry, Texas Tech University;  
Feb. 1988 M.S. (Organic Chemistry), Department of Chemistry, Chungnam Nat’l University; 
Feb. 1986 B.S. Department of Chemistry Education, Kongju Nat’l University.
Main Research Interests: 
Synthesis of Drug Delivery System, Alzheimer disease detection and treatment, Host-Guest Chemistry, Calixarene Chemistry, Chemosensors.
Research Accomplishment: Total SCI publications: 530; Total citation number: 42,400; H-index: 106 (Google scholar); Total number of patents registered: 80

Abstract:Breast cancer consists of heterogenic subpopulations, which determine the prognosis and response to chemotherapy. Among these subpopulations, a very limited number of cancer cells are particularly problematic. These cells, known as breast cancer stem cells (BCSCs), are thought responsible for metastasis and recurrence. They are thus major contributor to the unfavorable outcomes seen for many breast cancer patients. BCSCs are more prevalent in the hypoxic niche. This is an oxygen-deprived environment that is considered crucial to their proliferation, stemness, and self-renewal, but also one that makes BCSCs highly refractory to traditional chemotherapeutic regimens. Here we report a small molecule construct, AzCDF, that allows the therapeutic targeting of BCSCs and which is effective in normally refractory hypoxic tumor environments. A related system, AzNap, has been developed that permits CSC imaging. Several design elements are incorporated into AzCDF, including the CAIX inhibitor, acetazolamide (Az) to promote localization in MDA-MB-231 CSCs, a dimethylnitrothiophene subunit as a hypoxia trigger, and a 3,4-difluorobenzylidene curcumin (CDF) as a readily released therapeutic payload. This allows AzCDF to serve as a hypoxia-liable molecular platform that targets BCSCs selectively that decreases CSC migration, retards tumor growth, and lowers tumorigenesis rates as evidenced by a combination of in vitro and in vivo studies.

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