Cancer-associated proliferating cell nuclear antigen (caPCNA) (caPCNA)

Cancer-associated proliferating cell nuclear antigen (caPCNA) is a post-translationally modified isoform of the PCNA protein that is uniquely expressed in malignant cells across various cancer types [1][2]. While standard PCNA is essential for DNA replication and repair in all proliferating cells, the caPCNA variant possesses a distinct structural conformation that makes it a selective therapeutic target [3][4]. This isoform is characterized by specific modifications, such as methyl esterification, which create a targetable surface not present in the PCNA found in healthy cells [2]. Therapeutic agents like AOH1996 exploit this difference by binding to caPCNA and disrupting its ability to resolve conflicts between DNA replication and transcription [1][5]. This disruption leads to the accumulation of DNA damage, specifically double-strand breaks, and triggers apoptosis in cancer cells while sparing normal tissue [1]. Consequently, caPCNA is being investigated as a 'pan-cancer' target due to its broad expression in solid tumors and its potential for high selectivity and low toxicity [5][6].

Other names

Cancer-specific PCNAcaPCNAcsPCNAProliferating cell nuclear antigen isoform

Small molecule inhibition of the cancer-associated isoform of PCNA (caPCNA), which disrupts the protein's ability to coordinate DNA replication and repair. Specifically, drugs like AOH1996 bind to a unique hydrophobic pocket on caPCNA, leading to the collapse of replication forks and the induction of transcription-replication conflicts, ultimately resulting in selective apoptosis of cancer cells [1][5].