A Rofecoxib-Derived Theranostic Probe and Its Combination With PD-1 Inhibitor for High-Efficiency Cancer Therapy

Area of Science:

• Oncology
• Molecular Imaging
• Drug Development

Background:

• Precision oncology faces challenges in developing theranostic probes for tumor-specific targeting and efficacy.
• Cyclooxygenase-2 (COX-2) is a validated target in cancer therapy.

Purpose of the Study:

• To develop a novel COX-2 targeted fluorescent probe for enhanced tumor visualization and therapeutic intervention.
• To evaluate the monotherapy and combination therapy efficacy of the developed probe.

Main Methods:

• Synthesis of a Rofecoxib-derived COX-2 targeted probe (Compound 2).
• Assessment of Compound 2's fluorescence enhancement upon COX-2 binding in vitro.
• Evaluation of Compound 2 monotherapy and combination therapy with a PD-1 inhibitor in vivo.

Main Results:

• Compound 2 demonstrated a sixfold fluorescence enhancement upon COX-2 binding with minimal background.
• Compound 2 monotherapy resulted in 53% tumor regression.
• Combination therapy with a PD-1 inhibitor achieved 95% tumor regression by blocking COX-2/PGE2 and PD-1/PD-L1 pathways.

Conclusions:

• The developed COX-2 targeted probe offers improved tumor visualization and therapeutic potential.
• Concurrent blockade of COX-2/PGE2 and PD-1/PD-L1 axes significantly enhances anti-tumor efficacy.
• This theranostic approach provides a promising strategy for advancing cancer diagnosis and treatment.