Predicting response to neoadjuvant chemoradiotherapy in rectal cancer: from biomarkers to tumor models

Colorectal cancer (CRC) is a major contributor to cancer-associated morbidity worldwide and over one-third of CRC is located in the rectum. Neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection is commonly applied to treat locally advanced rectal cancer (LARC). In this review, we summarize current and novel concepts of neoadjuvant therapy for LARC such as total neoadjuvant therapy and describe how these developments impact treatment response. Moreover, as response to nCRT is highly divergent in rectal cancers, we discuss the role of potential predictive biomarkers. We review recent advances in biomarker discovery, from a clinical as well as a histopathological and molecular perspective. Furthermore, the role of emerging predictive biomarkers derived from the tumor environment such as immune cell composition and gut microbiome is presented. Finally, we describe how different tumor models such as patient-derived cancer organoids are used to identify novel predictive biomarkers for chemoradiotherapy (CRT) in rectal cancer.

Automated summary

Colorectal cancer is a major global contributor to cancer-related morbidity, with over one-third of cases located in the rectum. Neoadjuvant chemoradiotherapy followed by surgical resection is commonly used for locally advanced rectal cancer. This review summarizes current and novel concepts in neoadjuvant therapy for rectal cancer, discusses potential predictive biomarkers, and explores recent advances in biomarker discovery from clinical, histopathological, and molecular perspectives. The role of emerging predictive biomarkers from the tumor environment, such as immune cell composition and gut microbiome, is also presented.