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Advisor: Dr. Mark Tang
Develop a therapeutical strategy to overcome the drug resistance in breast cancer
Triple-negative breast cancer (TNBC) is a subtype of breast cancer and accounts for 15% ~ 20% of overall breast cancer cases and exhibits earlier age of onset, high metastasis, and aggressiveness with poor clinical outcomes shown by higher relapse and lower survival rates than other types of breast cancer. Currently, TNBC patients' treatments are still limited to surgery, chemotherapy, or radiation since the absence of cell receptors makes targeted hormonal therapies impossible. Novel targeted strategies are urgently needed. Targeting cysteine-dependence is an emergent strategy to treat mesenchymal TNBC. However, many TNBC cells are non-mesenchymal and irresponsive to cysteine deprivation. We aimed to develop a therapeutical strategy to overcome such resistances by epigenetic compound library screening. We found several potent compounds can synergize with cysteine deprivation to efficiently eliminate the non-mesenchymal TNBC. We further performed the transcriptomic profiling analysis to understand the underlying mechanism of the synthetic lethality of compounds. Overall, potent compounds/sensitizers identified in this study can overcome the drug resistance in non-mesenchymal tumor cells, which makes the targeted cysteine-dependence therapy applicable in various subtypes of breast cancer.
Advisor: Dr. Mark Tang
Exploring Alternative Approach for Pancreatic Cancer Therapy by Targeting Cysteine Metabolism
Cancer is a multifactorial disease, which involves dysfunction of normal cells and leads to uncontrollable growth and metastasis. Current cancer therapies often face the problem of being non-specific and harm also normal cells, this is especially a problem when cancers appear in vital organs. Pancreatic cancer is such type of cancer in close proximity to other vital organs, which makes it hard to be treated by traditional cancer therapies and also highly metastatic. Pancreatic cancer is one of the deadliest cancers although its incidence rate is relatively low. Cancer metabolism has been suggested recently as a promising target for cancer therapy, since cancer cells acquire differential cellular metabolism to proliferate much faster in contrast to normal cells. One novel cell death pathway that has recently been gained many interests is ferroptosis: an iron-dependent cell death characterized by the accumulation of lipid peroxides. Glutathione, derived from amino acid cysteine, is crucial to protect cells from lipid peroxidation. We are trying to explore the application of targeting cysteine metabolism therapy in pancreatic cancer and to understand underlying mechanisms involved in drug sensitivity and resistance.
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Zoom Link: https://michigantech.zoom.us/j/85937074602
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