Adenovirus E1A protein sensitizes chemotherapy-resistant tumors to cisplatin

Cisplatin resistance remains a critical obstacle in surgical oncology, with treatment failure exceeding 60% in recurrent solid tumors. The adenovirus type 5 early region 1A (E1A) protein demonstrates remarkable chemosensitization through p53-dependent and independent pathways, achieving 10-fold enhanced cisplatin sensitivity in resistant cell lines. Clinical trials combining E1A-expressing oncolytic adenoviruses with cisplatin show response rates of 63% versus 30-40% for chemotherapy alone. E1A restores apoptotic responses through p19ARF/p53 signaling, nuclear factor-kappaB inhibition, and CtBP corepressor interactions. Integration with surgical cytoreduction offers promise for neoadjuvant tumor downstaging and adjuvant micrometastatic elimination. Despite immunogenicity challenges, E1A-based viral therapeutics represent a mechanistically validated approach warranting inclusion in multimodal treatment strategies for chemotherapy-resistant cancers.