Accueil > Agenda > Max WICHA, University of Michigan Comprehensive Cancer Center, USA
Max WICHA, University of Michigan Comprehensive Cancer Center, USA
Friday 19 March 2021
We are honored to welcome on Friday 19th of March at 3 PM, Maw WICHA (University of Michigan Comprehensive Cancer Center, USA) for webinar entitled :
“Metabolic and Immunologic Targeting of Breast Cancer Stem Cells”
Breast cancers display a hierarchal organization and are driven by a subset of cells that display stem cell properties. These cells mediate metastasis and contribute to treatment resistance. These cancer stem cells (CSC’s) display a high degree of epigenetic plasticity allowing them to transition between proliferative epithelial states characterized by expression of aldehyde dehydrogenase (ALDH) and more mesenchymal invasive states characterized by a CD44+/CD24- phenotype. The transition between CSC states is regulated by the tumor microenvironment ,including nutrient availability, hypoxia and ROS levels. We have developed fluorescent reporter systems to characterize EMT/MET CSC cell state transitions and have utilized them to track CSC during tumor metastasis in Zebrafish models. We have also developed microfluidic devices that allow for capture and single cell molecular analysis of circulating tumor cells from breast cancer patients . We find evidence of EMT and MET circulating tumor cells (CTC’s) , in both single cells and tumor cell clusters isolated from breast cancer mouse xenographs and patients.
We have developed strategies to target CSC states by exploiting metabolic and immunologic vulnerabilities of these cells. Metabolic targeting involves NQO1 ROS generation combined with inhibition of superoxide dismutase(SOD).
CSC utilize multiple mechanisms for immune evasion. We have developed a strategy for immunologic targeting of CSC, utilizing nanodisc vaccines loaded with peptides derived from ALDH or SOX2.
Together these strategies have the potential to effectively target breast CSC improving patient outcome.
Luo et al Targeting Breast Cancer Stem Cell State Equilibrium through modulation of Redox Signalling Cell Metabolism 2018 28:1 2018
Luo and Wicha Targeting Cancer Stem Cell Redox Metabolism to Enhance Therapy Response Semin Raiat Oncol 2019 Jan 29(1) 42
Cheng et al Hydro-Seq enables contamination free hiogh throughput single cell RNA sequencing for circulation tumor cells Nature Communications 10 2163 2019
Najafabadi et al Cancer Immunotherapy via Targeting Cancer Stem Cells Using Vaccine Nanodiscs Nano Lett. Oct14 ;20(10):7783 2020
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