Measurement of copy number of ACTN4 to optimize the therapeutic strategy for locally advanced pancreatic cancer

摘要

The standard therapeutic strategy recommended for locally advanced pancreatic cancer (LAPC) is typically chemotherapy or chemoradiotherapy (CRT). Although the clinical benefit of chemotherapy alone versus CRT for LAPC has been compared in a number of clinical trials, the optimal therapy for LAPC remains unclear. Moreover, the clinical benefit derived from treatment in each clinical trial is a matter of controversy, and the superiority of one treatment over another has yet to be definitively demonstrated. The poor outcomes seen among patients with LAPC owe largely to the emergence of metastatic disease; therefore, accurately evaluating occult distant metastasis before choosing a therapeutic strategy could be expected to help stratify patients with LAPC into the most appropriate treatment regimen, namely local control or systemic therapy. In 1998, we identified the actinin-4 gene (ACTN4) as an actin-binding protein and showed its molecular mechanisms had clinical implications for cancer metastasis. We also identifiedACTN4gene amplification in pancreatic, ovarian, and salivary gland cancer, and demonstrated its utility as a strong prognostic biomarker for stage I lung adenocarcinoma in patients who had never received chemotherapy. Moreover, we recently reported thatACTN4gene amplification could be a useful biomarker for predicting the efficacy of CRT for LAPC. In the present review, we summarize current knowledge regarding therapeutic strategies for LAPC and discuss the potential development of personalized medicine usingACTN4measurement for patients with LAPC.