Disrupting SOX2 Self-Association and Condensates to Overcome Chemotherapeutic Drug Resistance in Lung Squamous Cell Carcinoma [Cut & Run, 2]

The high frequency of SOX2 copy number amplification observed in LSCC patients underscores its potential role as a regulator in this context. Our investigation reveals a strong correlation between SOX2 amplification and expression levels in LSCC patients.

Notably, overexpression of SOX2 confers resistance to chemotherapeutic drugs in LSCC cell lines. We elucidate that SOX2 undergoes phase separation, forming condensates that sequester chemotherapeutic agents used in LSCC treatment, thereby exacerbating chemotherapeutic drug resistance in LSCC cells. To address this, we design a small peptide containing 16 amino acids conjugated with 8 arginine, specifically targeting α-helix within HMG domain to disrupt SOX2 self-association.