Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical...

Area of Science:

• Oncology
• Pharmacology
• Biomedical Engineering

Background:

• Drug-resistant cancer phenotypes pose a significant challenge in anti-cancer therapy.
• Cancer stem cells (CSCs) are implicated in the development of chemoresistance.
• Targeting CSCs is crucial for improving treatment efficacy and preventing relapse.

Purpose of the Study:

• To investigate the efficacy of a combinatorial anti-inflammatory treatment (doxorubicin and aspirin) in reducing chemoresistance.
• To evaluate the impact of this treatment on cancer stem cell populations.
• To utilize a preclinical microfluidic model for predicting treatment outcomes.

Main Methods:

• A preclinical microfluidic model was used to test doxorubicin and aspirin (DA) combination therapy.
• The model incorporated cancer cell lines and patient-derived circulating tumor cell clusters.
• Treatment efficacy was assessed by measuring cell killing, apoptosis, CSC proportion, and colony-forming ability.

Main Results:

• Low-dose doxorubicin combined with aspirin demonstrated enhanced cancer cell killing and apoptosis.
• Seven-day DA treatment significantly reduced CSCs and colony-forming ability.
• Patient-derived samples showed variable responses, with a majority exhibiting increased efficacy or CSC reduction.

Conclusions:

• The doxorubicin-aspirin combination shows promise in reducing cancer stem cell generation and chemoresistance.
• This approach may help mitigate cancer relapse by targeting stressful stimuli-induced CSCs.
• Patient-derived models are essential for personalized drug discovery and treatment strategies.