Investigating Cisplatin Resistance in Squamous Cervical Cancer: Proteomic Insights into DNA Repair Pathways and Omics-Based Drug Repurposing

Cisplatin-based chemotherapy is a cornerstone in treating cervical cancer, yet the efficacy is frequently limited by the rapid onset of drug resistance, a major challenge in clinical management. To investigate this, we employed HPV16+ human cervix squamous carcinoma cells, SiHa (CIS/S), and their cisplatin-resistant subline (CIS/R) as a model. Using DIA-based proteomics, we identified 5152 protein groups and over 50,000 peptides with a global FDR in vitro validation. Cabozantinib and sorafenib gave us positive results in terms of increasing the cisplatin sensitivity of CIS/R cells. In conclusion, our findings provide insights into the molecular mechanisms underpinning cisplatin resistance in cervical cancer and propose novel strategies for combating this resistance through targeted therapies and drug repurposing.