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SPR965, a Dual PI3K/mTOR Inhibitor, as a Targeted Therapy in Ovarian Cancer

Arthur-Quan Tran1, Stephanie A Sullivan1, Leo Li-Ying Chan2

  • 1Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Frontiers in Oncology
|March 4, 2021
PubMed

Insights

SPR965, a PI3K/mTOR inhibitor, effectively reduced ovarian cancer cell proliferation and tumor growth in preclinical models. It warrants further investigation as a targeted therapy for ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Serous ovarian cancer remains a leading cause of cancer-related mortality.
  • Targeted therapies inhibiting the PI3K/AKT/mTOR pathway show promise.
  • SPR965 is a novel inhibitor of PI3K and mTOR C1/C2.

Purpose of the Study:

  • To evaluate the anti-tumorigenic effects of SPR965 in human serous ovarian cancer.
  • To investigate the impact of SPR965 on cell proliferation and tumor growth in vitro and in vivo.
  • To elucidate the molecular mechanisms underlying SPR965's anti-cancer activity.

Main Methods:

  • In vitro studies using human serous ovarian cancer cell lines.
  • In vivo studies utilizing a transgenic mouse model of high-grade serous ovarian cancer (KpB model).
  • Analysis of cell cycle, apoptosis, protein expression (p-AKT, p-S6, Ki67, VEGF, Bip), and epithelial-mesenchymal transition (EMT).

Main Results:

  • SPR965 demonstrated significant anti-proliferative activity, inducing cell cycle arrest and cellular stress.
  • SPR965 treatment markedly inhibited tumor growth in the KpB mouse model.
  • Downregulation of p-AKT, p-S6, Ki67, and VEGF, with upregulation of Bip, was observed.
  • SPR965 inhibited adhesion and invasion by modulating EMT.

Conclusions:

  • SPR965 exhibits potent anti-tumorigenic effects against serous ovarian cancer in vitro and in vivo.
  • SPR965 targets key signaling pathways including PI3K/AKT/mTOR and EMT.
  • SPR965 represents a promising targeted therapeutic agent for future ovarian cancer clinical trials.
Keywords:
SPR965cell proliferationcell stressinvasionovarian cancer

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