Objective:

To synthesize current knowledge on the expression landscape, oncogenic functions, molecular mechanisms, and clinical significance of ERCC6L in cancer.

Approach:

• Literature Review: A structured literature search was conducted using PubMed and Web of Science databases for articles published up to May 2026.

Key Findings:

• ERCC6L is frequently overexpressed in most tumor types, including breast cancer, hepatocellular carcinoma, lung adenocarcinoma, and gastric cancer, compared to normal tissues, driven by DNA amplification and promoter hypomethylation.
• High ERCC6L expression correlates with aggressive clinicopathological features, including advanced tumor stage, metastasis, and poor prognosis.
• ERCC6L promotes malignant phenotypes by accelerating cell cycle, exerting anti-apoptotic effects, and enhancing invasion and metastasis.
• Mechanistically, ERCC6L interacts with mitotic regulators and activates pro-survival signaling pathways, linking it to radio- and chemoresistance.
• ERCC6L is associated with an immunosuppressive tumor microenvironment, suggesting its potential as a predictive biomarker for immunotherapy.

Interpretation:

The consistent association of ERCC6L with aggressive tumor behavior positions it as a valuable prognostic biomarker and a promising therapeutic target.

Limitations:

• Current evidence is limited to in vitro and xenograft models, and further validation is required before clinical translation.

Conclusion: