Links between Biology, Prognosis and Prediction of Response to Chemotherapy in Colorectal Cancer

Abstract

Compared with the progress achieved in breast cancer, the use of prognostic and predictive parameters in colorectal cancer is lagging behind. One of the reasons is the limited information provided by ‘classic’ mutations as markers for response to therapy. To bridge this gap, prospective clinical trials need to be conducted to evaluate the usefulness of gene expression profiling and candidate markers, such as DNA repair proteins, onset of the methylator phenotype, neo-angiogenetic pathways related to inflammation, matrix metalloproteinases, tumor suppressors and cell signaling pathways (e.g. Akt). In parallel, the unrivalled sensitivity of molecular techniques may be applied to diagnostic parameters, such as cytokeratin 20 mRNA, for the detection of lymph node metastases. This article reviews the current knowledge on prognostic and predictive parameters in order to highlight the close link between tumor biology and tumor pharmacology. The increasing number of candidate markers together with recently introduced therapeutic options offer novel opportunities for a stepwise approach to the ambitious goal of individualized therapy in colorectal cancer.

Measurement of DPD and TS Transcripts Aimed to Predict Clinical Benefit from Fluoropyrimidines: Confirmation of the Trend in Russian Colorectal Cancer Series and Caution Regarding the Gene Referees

“…Secondly, the choice of TS/SDHA and DPD/SDHA ratio threshold between low and high expressors was done a posteriori, which increases the probability of data overinterpretation. At the same time, the conclusions of our study are in good agreement with most literature data [1][2][3][4][5][6][7][8][9][10][11]. Given the existence of racial and/or ethnic variations in the drug response [23], our data, which were the first to be obtained in Russian patients, add to the overall judgment on clinical significance of TS and DPD.…”

“…An increased content of DPD, which is a key enzyme for the 5-FU inactivation pathway, results in low intratumoral concentrations of fluoropyrimidines thus abolishing their cytotoxic action. Although the predictive role of TS and DPD is still a subject of noticeable controversy, most of the so far published studies support the clinical significance of these molecules [1][2][3][4][5][6][7][8][9][10][11]. Recently, the results of the first prospective study which tailored the choice of colorectal cancer therapy to the TS and DPD levels have been published.…”

Bevacizumab Improves the Overall and Progression-Free Survival of Patients with Metastatic Colorectal Cancer Treated with 5-Fluorouracil-Based Regimens Irrespective of Baseline Risk

“…It is possible that Köhne’s model may be refined by including additional parameters [9] and improving the predictive prognostic value of the model. Such factors could include recently proposed molecular markers including loss of heterozygosity, microsatellite instability, the presence of oncogenes and thymidylate synthase levels (for patients receiving 5-FU) [20,21,22]. …”

Genotyping of CYP3A5 Polymorphisms among Bulgarian Patients with Sporadic Colorectal Cancer and Controls

“…Colorectal cancer is one of the most common human neoplasias and is a leading cause of cancer-related morbidity and mortality [1,2]. It predominantly affects elderly people, equally women and men [3].…”