Predictive biomarker for efficient adjuvant therapies by evaluating metastatic ability

Abstract

Adjuvant chemotherapy is performed with the aim of preventing late metastasis; however, if the primary tumor is completely resected initially, the development of late metastases most likely depends on the characteristic metastatic activity of the tumor. In other words, it may be that the best strategies for adjuvant chemotherapy could be established if the molecular biological profiles of primary tumor characteristics are determined.
We isolated the actin-bundling molecule alpha-actinin-4 （ACTN4） from gene amplification in highly metastatic breast cancer, colorectal cancer, ovarian cancer, pancreatic cancer, lung cancer, salivary gland cancer, and tongue cancer. High expression of the ACTN4 protein induces the formation of cell processes that are involved in cancer metastasis. In a transcriptome subgroup analysis of a randomized controlled study of adjuvant chemotherapy for non-small cell lung cancer conducted in Canada, an additional effect from adjuvant chemotherapy was demonstrated only in a group with high ACTN4 expression. We developed a FISH probe that detects gene amplification of ACTN4 and began the clinical development of biomarkers that predict the metastatic activity of stage I lung adenocarcinoma and contribute to providing appropriate adjuvant chemotherapy.
Non-small cell lung cancer is not the only cancer in which late metastasis can be predicted from gene amplification. For oral cancer as well, it may be possible to provide appropriate therapeutic strategies by identifying high-risk groups for late metastasis. Here, we discuss the clinical significance of these biomarkers.