A Multimodal Approach to Discover Biomarkers for Taxane-Induced Peripheral Neuropathy (TIPN): A Study Protocol.
A Multimodal Approach to Discover Biomarkers for Taxane-Induced Peripheral Neuropathy (TIPN): A Study Protocol.
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DOI：
10.1177/15330338221127169
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发表时间：
2022-01
影响因子：
2.8
通讯作者：
中科院分区：
文献类型：
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前言：紫杉烷是一类常用的化疗药物，用于治疗各种实体肿瘤，包括乳腺癌和卵巢癌。紫杉烷诱导的周围神经病变(TIPN)在高达70%的患者中发生，在治疗过程中和治疗后都会影响生活质量。TIPN通常表现为手足刺痛和麻木，并可导致不可逆转的周围神经功能丧失。TIPN可能是剂量受限的，可能会影响临床结果。TIPN背后的机制还知之甚少。因此，治疗选择有限，也没有工具可以及早发现那些将发展为TIPN的人。尽管一些患者可能有遗传易感性，但遗传生物标记物在预测化疗引起的周围神经病变(CIPN)方面一直不一致。此外，其他分子标志物(如代谢物、mRNA、miRNA、蛋白质)可能对预测CIPN提供信息，但在很大程度上仍未被探索。我们预计，需要多个生物标志物的组合才能一致地预测那些将发生TIPN的人。方法：为了解决识别TIPN风险患者的这一临床空白，我们启动了CIPN遗传学和炎症标记物(GENIE)研究。这项纵向多中心观察研究使用一种新的多模式方法来评估400名乳腺癌患者在紫杉烷治疗之前、期间和之后的基因组变异、代谢物、DNA甲基化、基因表达和循环细胞因子/趋化因子。分子和患者报告的数据将在紫杉烷治疗之前、期间和之后收集。多模式数据将用于开发一套全面的TIPN预测生物标志物特征。结论：本研究的目的是能够及早发现有发生TIPN风险的患者，提供一种工具来改进紫杉烷治疗以减少TIPN的发病率，并提高患者的生活质量。本文简要回顾了CIPN和TIPN的研究现状，并介绍了GINIE研究设计。
Introduction: Taxanes are a class of chemotherapeutics commonly used to treat various solid tumors, including breast and ovarian cancers. Taxane-induced peripheral neuropathy (TIPN) occurs in up to 70% of patients, impacting quality of life both during and after treatment. TIPN typically manifests as tingling and numbness in the hands and feet and can cause irreversible loss of function of peripheral nerves. TIPN can be dose-limiting, potentially impacting clinical outcomes. The mechanisms underlying TIPN are poorly understood. As such, there are limited treatment options and no tools to provide early detection of those who will develop TIPN. Although some patients may have a genetic predisposition, genetic biomarkers have been inconsistent in predicting chemotherapy-induced peripheral neuropathy (CIPN). Moreover, other molecular markers (eg, metabolites, mRNA, miRNA, proteins) may be informative for predicting CIPN, but remain largely unexplored. We anticipate that combinations of multiple biomarkers will be required to consistently predict those who will develop TIPN. Methods: To address this clinical gap of identifying patients at risk of TIPN, we initiated the Genetics and Inflammatory Markers for CIPN (GENIE) study. This longitudinal multicenter observational study uses a novel, multimodal approach to evaluate genomic variation, metabolites, DNA methylation, gene expression, and circulating cytokines/chemokines prior to, during, and after taxane treatment in 400 patients with breast cancer. Molecular and patient reported data will be collected prior to, during, and after taxane therapy. Multi-modal data will be used to develop a set of comprehensive predictive biomarker signatures of TIPN. Conclusion: The goal of this study is to enable early detection of patients at risk of developing TIPN, provide a tool to modify taxane treatment to minimize morbidity from TIPN, and improved patient quality of life. Here we provide a brief review of the current state of research into CIPN and TIPN and introduce the GENIE study design.
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影响因子：
6.7
作者：
Chua KC;Xiong C;Ho C;Mushiroda T;Jiang C;Mulkey F;Lai D;Schneider BP;Rashkin SR;Witte JS;Friedman PN;Ratain MJ;McLeod HL;Rugo HS;Shulman LN;Kubo M;Owzar K;Kroetz DL
通讯作者：
Kroetz DL
影响因子：
11.2
作者：
Beutler, Andreas S.;Kulkarni, Amit A.;Kanwar, Rahul;Klein, Christopher J.;Therneau, Terry M.;Qin, Rui;Banck, Michaela S.;Boora, Ganesh K.;Ruddy, Kathryn J.;Wu, Yanhong;Smalley, Regenia L.;Cunningham, Julie M.;Le-Lindqwister, Nguyet Anh;Beyerlein, Peter;Schroth, Gary P.;Windebank, Anthony J.;Zuechner, Stephan;Loprinzi, Charles L.
通讯作者：
Loprinzi, Charles L.
影响因子：
3.1
作者：
CHAVES, JF;BROWN, JM
通讯作者：
BROWN, JM
影响因子：
3
作者：
Chandereng, Thevaa;Gitter, Anthony
通讯作者：
Gitter, Anthony
影响因子：
4.4
作者：
Boora GK;Kulkarni AA;Kanwar R;Beyerlein P;Qin R;Banck MS;Ruddy KJ;Pleticha J;Lynch CA;Behrens RJ;Züchner S;Loprinzi CL;Beutler AS
通讯作者：
Beutler AS