INCENP and CDCA8 predict neoadjuvant chemotherapy response and outcomes in esophageal squamous cell carcinoma

Neoadjuvant chemotherapy (NACT), a key strategy for various cancers, markedly improves patient prognosis and 5-year survival rates. However, numerous patients develop resistance to NACT and thus fail to benefit from it. Therefore, identifying reliable biomarkers to predict patient responsiveness to NACT remains a critical challenge. Here, we demonstrate that elevated expression of INCENP and CDCA8 contributes to poor NACT responsiveness across multiple cancers. Mechanistically, the 5'UTR (GGACT at position 113) of INCENP and the 3'UTR (GGACT at position 1041) of CDCA8 undergo m⁶A methylation and are recognized by YTHDF3, which facilitates their translation through interaction with eIF3A, ultimately driving poor response to NACT. Moreover, inhibition of INCENP and CDCA8 enhances NACT sensitivity by promoting multipolar spindle formation. Collectively, our findings establish that INCENP and CDCA8 serve as crucial biomarkers for predicting NACT responsiveness and as potential therapeutic targets for combination therapy with NACT to improve patient survival.