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可切除胰腺癌个性化治疗的预测生物标志物

Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer.

作者信息

Merz Valeria, Mangiameli Domenico, Zecchetto Camilla, Quinzii Alberto, Pietrobono Silvia, Messina Carlo, Casalino Simona, Gaule Marina, Pesoni Camilla, Vitale Pasquale, Trentin Chiara, Frisinghelli Michela, Caffo Orazio, Melisi Davide

机构信息

Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy.

Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, Verona, Italy.

出版信息

Front Surg. 2022 May 4;9:866173. doi: 10.3389/fsurg.2022.866173. eCollection 2022.

Abstract

The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences disease relapse, even when a combination adjuvant therapy is offered. Therefore, aiming at improving disease free survival and overall survival of these patients, there is an increasing interest in evaluating the activity and efficacy of neoadjuvant and perioperative treatments. In this view, it is of utmost importance to find biomarkers able to select patients who may benefit from a preoperative therapy rather than upfront surgical resection. Defined genomic alterations and a dynamic inflammatory microenvironment are the major culprits for disease recurrence and resistance to chemotherapeutic treatments in pancreatic cancer patients. Signal transduction pathways or tumor immune microenvironment could predict early recurrence and response to chemotherapy. In the last decade, distinct molecular subtypes of pancreatic cancer have been described, laying the bases to a tailored therapeutic approach, started firstly in the treatment of advanced disease. Patients with homologous repair deficiency, in particular with mutant germline BRCA genes, represent the first subgroup demonstrating to benefit from specific therapies. A fraction of patients with pancreatic cancer could take advantage of genome sequencing with the aim of identifying possible targetable mutations. These genomic driven strategies could be even more relevant in a potentially curative setting. In this review, we outline putative predictive markers that could help in the next future in tailoring the best therapeutic strategy for pancreatic cancer patients with a potentially curable disease.

摘要

对于可立即切除的胰腺癌患者,主要治疗方法仍然是先行手术,这是唯一可能治愈的策略。然而,大多数接受胰腺癌手术切除的患者即使接受了辅助联合治疗,仍会出现疾病复发。因此,为了提高这些患者的无病生存期和总生存期,人们对评估新辅助治疗和围手术期治疗的活性和疗效越来越感兴趣。从这个角度来看,找到能够选择可能从术前治疗而非先行手术切除中获益的患者的生物标志物至关重要。明确的基因组改变和动态的炎症微环境是胰腺癌患者疾病复发和对化疗耐药的主要原因。信号转导通路或肿瘤免疫微环境可以预测早期复发和对化疗的反应。在过去十年中,已经描述了胰腺癌的不同分子亚型,为量身定制的治疗方法奠定了基础,这种方法首先从晚期疾病的治疗开始。同源修复缺陷的患者,特别是具有种系BRCA基因突变的患者,是第一个显示从特定治疗中获益的亚组。一部分胰腺癌患者可以利用基因组测序来识别可能的可靶向突变。这些基于基因组的策略在潜在治愈的情况下可能更具相关性。在这篇综述中,我们概述了可能的预测标志物,这些标志物可能在未来帮助为患有潜在可治愈疾病的胰腺癌患者量身定制最佳治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8654/9114435/a39d7adb6cc8/fsurg-09-866173-g0001.jpg

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