Transcriptomic analysis in locally advances rectal cancer: could it still be a genomic tool to guide the neoadjuvant treatment?

SOLEDAD ISEAS; JUAN MARTÍN SENDOYA; MARIANA CORAGLIO; MARIANO GOLUBICKI; JUAN ROBBIO; UBALDO GUALDRINI; ANA CABANNE; MIRTA KUJARUK; VANESA MIKOLAITIS; MARIANA RIZZOLO; RUBEN SALANOVA; CECILIA ROTONDARO; MARTIN C. ABBA; OSVALDO LUIS PODHAJCER; ENRIQUE ROCA; ANDREA S. LLERA

Conferencia; Third Annual Advances in Colorectal Oncology, Memorial Sloan Kettering Cancer Center; 2018

Memorial Sloan Kettering Cancer Center

For locally advanced rectal cancer (LARC), preoperative chemoradiotherapy (CRT) induction chemotherapy(iCT) comprises the standard treatment. However, only 15% of patients achieve a pathological complete response, while 40% respond variably. This scenario poses a strong need for biomarkers able to predict response to CRT and provide guidance towards optimal treatment for each patient. Currently, there is a growing interest in immunotherapy-based on studying the complex association between immune components and oncologic outcomes. Evidence on immune contribution to radiation therapy effects has been suggested. Therefore, immune components have to be considered together with genetic features of the tumor in order to develop predictive biomarkers. Here we explore LARC gene expression data to identify baseline immune populations and pathways that might be associated with response to CRT.Examining the widely adopted scores available to evaluate patient response to CRT (CAP?s pTRG score, mrTRG and NAR), we understand that each score reflects different aspects of tumor response biology. This fact marks the need for improved, more comprehensive response scores. Higher expression ofimmune infiltrates related genes in conjunction with upmodulated pathways such as antigen processing and presentation by MHCI/II, and apoptotic response to DNA damage through TAP73 leads to speculate that good responding tumors might be more ?inflamed? but still subjected toimmunosuppressive mechanisms. Poor responders seem to reunite more ?immune desert? features, such as upregulation of βcatenin signaling pathways and proliferation-related transcription factors. Even considering the caveats regarding our current sample size, we were able to detect potentialsources for CRT response predictive biomarkers. With the necessary validation of these analyses underway, we envision this effort as the basis to evaluate genomic biomarkers for response prediction in our LARC population, in conjunction with mutational landscape analyses that are currently being performed.