What Biochemical and Molecular Biological Factors Have Greater Relevance to Treatment Decisions?

Abstract

All current treatments for rectal cancer come with a price to pay, namely, the risk for over - and undertreatment based on current treatment decisions leading to sometimes even unnecassary toxicities. Thus, it would further improve the results of both treatment outcome and quality of life, if we could better tailor the treatment for rectal cancer based on validated biochemical and molecular biological factors. It is clear that several already known tumor biological features have an important impact on the individual tumor responses to certain treatments. Thus, detection and analysis of these biomarkers will ultimately lead to better treatment decisions in all parts of the current treatment algorithm. However, most studies so far have been rather limited in its attempts to identify biomarker based predictors for e.g. response to CRT, surgical decisions and systemic therapy. Six genetic biomarkers were identified with the potential of being predictive in the outcome after CRT, like p53, EGFR, TYMS, Ki-67, p21 and bax-bcl-2. TYMS expression measurements seem to be worthwhile to further study in future trials, while survivin showed mostly conflicting results and gene expression profiles with microarrays need further validation with larger patient groups. Nevertheless, there is great interest in the identification of biochemical and molecular biological factors in treatment decision making and many promising developments are on the way, like whole genome DNA, RNA analysis, multiple mutation testing, full sequencing and the association of genotype with phenotype. However, before the first successful biomarker development can been finalized and implemented clinically, several collaborations and consecutively external validations still need to be completed.