(W0930-12-81) Combination Therapy for the Reversal of Multi-drug Resistant Cancer

Purpose: In recent times, the combined approach of photothermal therapy (PTT) and heat-shock protein (HSP) inhibition has been widely applied. However, optimizing the timing of PTT and HSP inhibitor application can be challenging and tumor recurrence after PTT remains a significant hurdle in achieving good survival outcomes.

Methods: In this study, we used a gold nanocluster (GNC) micelle system capable of multiple near-infrared (NIR) laser exposures. Through RNA-seq analysis, we identified that that repeated NIR exposure leads to the upregulation of HSP and cell cycle-related genes, which might be linked to tumor recurrence. To overcome these challenges, we presented an RNA-seq-guided drug combination strategy of GNC, docetaxel (DTX), and quercetin (QER) via a nanosystem.

Results: QER downregulated HSP expression and suppressed the function of P-glycoprotein with mild antitumor activity. Furthermore, DTX demonstrated antitumor activity with significant G2-M cell-cycle arrest. The co-administration of QER and DTX also inhibited the migration of cancer cells, indicating the possibility of suppressing metastasis. When all drugs were administered simultaneously in a triple combination, a very strong synergistic effect was achieved, as indicated through increased apoptosis induction and cell-cycle arrest in vitro and in vivo.

Conclusion: Therefore, we emphasize the necessity and importance of the triple combination nanosystem in inhibiting tumor recurrence and metastasis. In conclusion, the findings from our study highlight the advantages of triple combination and provide a potential translational direction for photothermal-chemotherapy. Furthermore, our study can serve as a good example of next generation sequencing-based cancer treatment and present a more patient-specific treatment.