GENUS ONCOLOGY - THE MUC1-C COMPANY
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Publication Category:
MUC1-C inhibitor formulated in Nanoparticles

(chronological order)
Intracellular targeting of the oncogenic MUC1-C protein with a novel GO-203 nanoparticle formulation
Clinical Cancer Research , 2015; 21(10):2338-2347; Hasegawa M, Sinha RK, Kumar M, Alam M, Yin L, Raina D, Kharbanda A, Panchamoorthy G, Gupta D, Singh H, Kharbanda S, and Kufe D.

click to see abstract

PURPOSE:
The MUC1-C oncoprotein is an intracellular target that is druggable with cell-penetrating peptide inhibitors. However, development of peptidyl drugs for treating cancer has been a challenge because of unfavorable pharmacokinetic parameters and limited cell-penetrating capabilities.
EXPERIMENTAL DESIGN:
Encapsulation of the MUC1-C inhibitor GO-203 in novel polymeric nanoparticles was studied for effects on intracellular targeting of MUC1-C signaling and function.
RESULTS:
Our results show that loading GO-203 into tetrablock polylactic acid (PLA)-polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG copolymers is achievable and, notably, is enhanced by increasing PEG chain length. In addition, we found that release of GO-203 from these nanoparticles is controllable over at least 7 days. GO-203/nanoparticle treatment of MUC1-C-positive breast and lung cancer cells in vitro was more active with less frequent dosing than that achieved with nonencapsulated GO-203. Moreover, treatment with GO-203/nanoparticles blocked MUC1-C homodimerization, consistent with on-target effects. GO-203/nanoparticle treatment was also effective in downregulating TIGAR, disrupting redox balance, and inhibiting the self-renewal capacity of cancer cells. Significantly, weekly administration of GO-203/nanoparticles to mice bearing syngeneic or xenograft tumors was associated with regressions that were comparable with those found when dosing on a daily basis with GO-203.
CONCLUSIONS:
These findings thus define an effective approach for (i) sustained administration of GO-203 in polymeric PLA-(PEG-PPG-PEG) nanoparticles to target MUC1-C in cancer cells and (ii) the potential delivery of other anticancer peptide drugs.


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  • Company
    • Mission
    • About Us
    • Genus Overview
    • Management
    • Board of Directors
    • Scientific Advisory Board
    • Clinical and Research Partners
    • Contact
    • Sitemap
  • Why Target MUC1-C?
  • Clinical Trials
    • Summary
    • GO-203
    • Phase 2 AML Clinical Trial
  • The Science
    • Overview
    • MUC1 in Human Cancer: The Numbers
    • MUC1 in Human Cancer: Overexpression
    • Target for Carcinoma Stem-Like Cell
    • Target for Leukemia Stem Cell
    • MUC1-C is an Attractive Target for Reversing Immune Evasion
    • Intellectual Property
  • Programs
    • Pipeline
    • Targeting the Cytoplasmic Domain
    • Targeting the Extracellular Domain
    • Biomarker Program
  • News & Publications
    • News
    • Publications >
      • Complete Listing
      • Role of MUC1-C in Signal Transduction
      • Role of MUC1-C in Epigenetic Regulation
      • Role of MUC1-C in Immune Evasion
      • MUC1 Vaccine
      • MUC1-C in Stem-like Cells
      • MUC1-C inhibitor formulated in Nanoparticles
      • MUC1-C inhibitor is synergistic with chemotherapeutic and targeted drugs
      • MUC1-C is a druggable target