Browsing by Subject "CSC"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Novel therapeutics and drug-delivery approaches in the modulation of glioblastoma stem cell resistance
    (T&F, 2022-04) Smiley, Shelby B.; Zarrinmayeh, Hamideh; Das, Sudip K.; Pollok , Karen E.; Vannier, Michael W.; Veronesi, Michael C.; Radiology and Imaging Sciences, School of Medicine
    Glioblastoma (GBM) is a deadly malignancy with a poor prognosis. An important factor contributing to GBM recurrence is high resistance of GBM cancer stem cells (GSCs). While temozolomide (TMZ), has been shown to consistently extend survival, GSCs grow resistant to TMZ through upregulation of DNA damage repair mechanisms and avoidance of apoptosis. Since a single-drug approach has failed to significantly alter prognosis in the past 15 years, unique approaches such as multidrug combination therapy together with distinctive targeted drug-delivery approaches against cancer stem cells are needed. In this review, a rationale for multidrug therapy using a targeted nanotechnology approach that preferentially target GSCs is proposed with discussion and examples of drugs, nanomedicine delivery systems, and targeting moieties.
  • Thumbnail Image
    Item
    A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-like Cells
    (Elsevier, 2019-03-12) Chefetz, Ilana; Grimley, Edward; Yang, Kun; Hong, Linda; Vinogradova, Ekaterina V.; Suciu, Radu; Kovalenko, Ilya; Karnak, David; Morgan, Cynthia A.; Chtcherbinine, Mikhail; Buchman, Cameron; Huddle, Brandt; Barraza, Scott; Morgan, Meredith; Bernstein, Kara A.; Yoon, Euisik; Lombard, David B.; Bild, Andrea; Mehta, Geeta; Romero, Iris; Chiang, Chun-Yi; Landen, Charles; Cravatt, Benjamin; Hurley, Thomas D.; Larsen, Scott D.; Buckanovich, Ronald J.; Department of Biochemistry and Molecular Biology, School of Medicine
    Summary Ovarian cancer is typified by the development of chemotherapy resistance. Chemotherapy resistance is associated with high aldehyde dehydrogenase (ALDH) enzymatic activity, increased cancer “stemness,” and expression of the stem cell marker CD133. As such, ALDH activity has been proposed as a therapeutic target. Although it remains controversial which of the 19 ALDH family members drive chemotherapy resistance, ALDH1A family members have been primarily linked with chemotherapy resistant and stemness. We identified two ALDH1A family selective inhibitors (ALDH1Ai). ALDH1Ai preferentially kills CD133+ ovarian cancer stem-like cells (CSCs). ALDH1Ai induce necroptotic CSC death, mediated, in part, by the induction of mitochondrial uncoupling proteins and reduction in oxidative phosphorylation. ALDH1Ai is highly synergistic with chemotherapy, reducing tumor initiation capacity and increasing tumor eradication in vivo. These studies link ALDH1A with necroptosis and confirm the family as a critical therapeutic target to overcome chemotherapy resistance and improve patient outcomes.