2. Academic Validation
  3. Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer

Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer

  • Cell Chem Biol. 2021 Aug 19;28(8):1206-1220.e6. doi: 10.1016/j.chembiol.2021.02.014.
Dhanir Tailor 1,  Angel Resendez 2,  Fernando Jose Garcia-Marques 3,  Mallesh Pandrala 1,  Catherine C Going 3,  Abel Bermudez 3,  Vineet Kumar 2,  Marjan Rafat 4,  Dhanya K Nambiar 2,  Alexander Honkala 2,  Quynh-Thu Le 2,  George W Sledge 5,  Edward Graves 6,  Sharon J Pitteri 3,  Sanjay V Malhotra 7
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA.
  • 2 Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
  • 3 Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
  • 4 Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37212, USA.
  • 5 Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
  • 6 Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
  • 7 Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA; Department of Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA. Electronic address: [email protected].
PMID: 33713600 DOI: 10.1016/j.chembiol.2021.02.014
Abstract

Y box binding protein 1 (YB-1) is a multifunctional protein associated with tumor progression and the emergence of treatment resistance (TR). Here, we report an azopodophyllotoxin small molecule, SU056, that potently inhibits tumor growth and progression via YB-1 inhibition. This YB-1 Inhibitor inhibits cell proliferation, resistance to Apoptosis in ovarian Cancer (OC) cells, and arrests in the G1 phase. Inhibitor treatment leads to enrichment of proteins associated with Apoptosis and RNA degradation pathways while downregulating spliceosome pathway. In vivo, SU056 independently restrains OC progression and exerts a synergistic effect with paclitaxel to further reduce disease progression with no observable liver toxicity. Moreover, in vitro mechanistic studies showed delayed disease progression via inhibition of drug efflux and multidrug resistance 1, and significantly lower neurotoxicity as compared with etoposide. These data suggest that YB-1 inhibition may be an effective strategy to reduce OC progression, antagonize TR, and decrease patient mortality.

Keywords

Y box binding protein 1; ovarian cancer; targeted therapy; treatment resistance.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-150231
    98.88%, YB-1 Inhibitor.