Molecular markers for response prediction in locally advanced rectal cancer. Is individualized therapy coming?

Based on the results of the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group preoperative 5-FU-based radiochemotherapy (RCTx) is recommended as the standard treatment of locally advanced rectal cancers (UICC stages II and III) of the middle and lower third of the rectum (0-12 cm above the anocutaneous margin). Unfortunately, tumor response to neoadjuvant RCTx is very heterogeneous ranging from complete pathological response (pCR) to total resistance. To fulfill the clinical requirement of an individualized and risk-adapted multimodal treatment, progress has been made in genomic and proteomic analyses of cellular signaling pathways. Compared with postoperatively determined clinicopathological parameters of local response, complex phenotypes, such as tumor responsiveness to RCTx do not depend on the expression levels of just one or a few genes and proteins. Therefore, methods which allow comprehensive interrogation of genetic pathways and networks hold great promise in delivering tumor-specific signatures, because expression levels of tens of thousands of genes can be monitored simultaneously. During the past few years microarray technology has emerged as the key tool in addressing pertinent clinical questions, the answers to which are critical for the realization of personalized genomic medicine, in which patients will be treated based on the biology of the tumor and the genetic profile.