Somatic pharmacogenomics in the treatment prognosis of locally advanced rectal cancer patients: a narrative review of the literature.

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Expert Review of Clinical Pharmacology Pub Date : 2024-08-01 Epub Date: 2024-07-24 DOI:10.1080/17512433.2024.2375449
Noemi Milan, Federico Navarria, Erika Cecchin, Elena De Mattia
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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.

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局部晚期直肠癌患者治疗预后的体细胞药物基因组学:文献综述。
简介:局部晚期直肠癌(LARC)患者的标准治疗包括使用氟嘧啶类药物的新辅助化放疗(nCRT),然后进行手术切除。新推出的治疗策略根据目前包括临床放射学标准而非分子变量的风险分层算法提出了强化治疗方案或更保守的方法。如何更好地对患者进行分层是一个亟待解决的临床问题,药物基因组学可能有助于确定新的遗传标记,并将其纳入临床算法,从而实现 nCRT 的个性化。一个新兴领域可能是将体细胞突变评估为与患者预后相关的潜在遗传标记。目前,RAS/BRAF 基因中的肿瘤突变以及微卫星不稳定性(MSI)状态已被用于结直肠癌(CRC)的治疗选择;然而,它们在 LARC 中的临床价值仍不明确:本文献综述讨论了主要癌基因RAS、KRAS、BRAF、PIK3CA、SMAD4和TP53突变的预后作用的相关研究结果,包括接受nCRT治疗的LARC患者的MSI状态:事实证明,KRAS是最有希望的标志物,它始终与较差的无病生存率和总生存率相关。因此,KRAS可能是将其纳入风险分层算法以制定个性化治疗的良好候选指标。
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来源期刊
Expert Review of Clinical Pharmacology
Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.30
自引率
2.30%
发文量
127
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.
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