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