Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. (May 2022) - Nikolic, Aleksandra
Abstract: The progress that has been made in the treatment of rectal cancer has mostly resulted from multimodality strategy approach that combines surgery, chemotherapy and radiotherapy. In locally advanced rectal cancer (LARC), surgery remains the primary treatment, while neoadjuvant chemoradiotherapy (nCRT) is used to downsize or downstage the tumor before surgical resection. Highly variable response to nCRT observed in LARC patients raises the need for biomarkers to enable prediction and evaluation of treatment response in a more efficient and timely manner than currently available tools. The search for predictive biomarkers continues beyond blood proteins, which have failed in subsequent validation studies. This review presents nucleic acids-based markers and their predictive potential in LARC patients. Most of the candidate biomarkers come from relatively small single-institution studies. The only candidate biomarker that emerged as relevant in more than a single study was elevated levels of Fusobacterium nucleatum nucleic acids in tumor tissue. Considering that this marker is easily accessible through non-invasive analysis of faecal samples, its predictive potential is worth further validation. The other candidate nucleic acid-based biomarkers require more consistent studies on larger cohorts before they can be considered for use in clinical setting. Highlights: Nucleic acids are promising biomarkers for response to therapy in colorectal cancer. Most candidate biomarkers come from relatively small single-institution studies. Circulating tumor DNA has predictive value, but requires complex and costly analysis. Levels of F. nucleatum nucleic acids in tumor tissue appear to have predictive value. Non-invasive low-cost test could be developed for F. nucleatum nucleic acids.