Molecular analyses of peritoneal metastasis from colorectal cancer

Abstract

Background: Despite a trend showing continued improvement in survival by combing targeted agents for colorectal cancer (CRC), the improvement observed is limited. Moreover, clinically relevant benefits were not achieved in peritoneal metastasis cases. The role of cytoreductive surgery (CRS) and the benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) have been questioned. This review aimed to provide an overview of the current status of the studies reporting on the molecular knowledge of peritoneal metastasis from CRC (CRC-PM).Current Concepts: The PRODIGE 7 study was performed to assess the specific contributions of HIPEC to the survival benefit in CRC-PM cases by comparing CRS treatment alone and CRS with oxaliplatin-based HIPEC. However, this study did not reveal any survival improvement, and oxaliplatin resistance was suggested as the main cause of this negative outcome. Hence, the relative resistance to oxaliplatin in consensus molecular subtype (CMS) 4 CRC is of great interest.Discussion and Conclusion: Recent treatments for metastatic CRC have gradually moved to precision medicine based on individual biological information through high-throughput technology, such as next-generation sequencing. In the transcriptome study, CRC-PM was identified as an almost homogeneous CMS4 classification, which is known to have strong resistance to oxaliplatin-based chemotherapy. These results suggest the need to clarify complex sub-signal transmission pathways derived from transcriptome or proteome studies of CRC-PM. Finally, to compare two studies, it is necessary to establish a representative patient group and consider standardized sample collection, treatment, and analysis.