Noemi Milan, Federico Navarria, Erika Cecchin, Elena De Mattia
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引用次数: 0
Abstract
Introduction: Standard treatment for patients with locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines, followed by surgical excision. The newly introduced therapeutic strategies propose intensified regimens or more conservative approaches based on risk stratification algorithms that currently include clinicoradiological criteria but not molecular variables. How to better stratify patients is a burning clinical question, and pharmacogenomics may prove useful in identifying new genetic markers that could be incorporated into clinical algorithms to personalize nCRT. An emerging area could be the evaluation of somatic mutations as potential genetic markers that correlate with patient prognosis. Tumor mutations in the RAS/BRAF genes, as well as microsatellite instability (MSI) status, are currently used in treatment selection for colorectal cancer (CRC); however, their clinical value in LARC is still unclear.
Area covered: This literature review discusses the relevant findings on the prognostic role of mutations in the key oncogenes RAS, KRAS, BRAF, PIK3CA, SMAD4 and TP53, including MSI status in LARC patients treated with nCRT.
Expert opinion: KRAS proved to be the most promising marker, consistently associated with poorer disease-free survival and overall survival. Therefore, KRAS could be a good candidate for integration into the risk stratification algorithm to develop a personalized treatment.
期刊介绍:
Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery.
Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.