Engineering high throughput screening platforms of cervical cancer

Area of Science:

• Biomedical Engineering
• Oncology
• Drug Discovery

Background:

• Cervical cancer is a leading cause of cancer death in young women, with high rates of recurrence and metastasis.
• Existing treatments have limited efficacy, and novel therapeutic development faces significant challenges.
• There is an urgent need for effective anticancer drugs and improved screening methods for cervical cancer patients.

Purpose of the Study:

• To develop and validate a novel multilayer multicellular platform for high-throughput drug screening.
• To simultaneously evaluate the anti-metastatic and anti-angiogenic efficacy of potential anticancer drugs.
• To facilitate the identification of novel therapeutics for cervical cancer.

Main Methods:

• A multilayer platform was created using human cervical cancer cell lines and primary human microvascular endothelial cells within hydrogel layers (collagen I, fibrinogen, fibronectin, GelMA, PEGDA).
• Design of experiments statistical optimization was used to determine optimal hydrogel compositions.
• The platform's performance was validated, and its viscoelastic properties were assessed.
• A targeted drug screen of four clinically relevant drugs was conducted on two cervical cancer cell lines using the optimized platform.

Main Results:

• Optimized hydrogel compositions were identified to maximize cervical cancer cell invasion and endothelial microvessel length.
• The validated platform demonstrated suitability for drug screening applications.
• A targeted screen identified potential efficacy of tested drugs against cervical cancer models.

Conclusions:

• The developed platform offers a valuable tool for screening large compound libraries for cervical cancer.
• This approach can aid in mechanistic studies, drug discovery, and the advancement of precision oncology for cervical cancer.
• The platform holds promise for accelerating the development of effective treatments for cervical cancer.