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成功预防和治疗乳腺癌的关键研究差距与转化优先事项

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.

作者信息

Eccles Suzanne A, Aboagye Eric O, Ali Simak, Anderson Annie S, Armes Jo, Berditchevski Fedor, Blaydes Jeremy P, Brennan Keith, Brown Nicola J, Bryant Helen E, Bundred Nigel J, Burchell Joy M, Campbell Anna M, Carroll Jason S, Clarke Robert B, Coles Charlotte E, Cook Gary J R, Cox Angela, Curtin Nicola J, Dekker Lodewijk V, Silva Isabel dos Santos, Duffy Stephen W, Easton Douglas F, Eccles Diana M, Edwards Dylan R, Edwards Joanne, Evans D, Fenlon Deborah F, Flanagan James M, Foster Claire, Gallagher William M, Garcia-Closas Montserrat, Gee Julia M W, Gescher Andy J, Goh Vicky, Groves Ashley M, Harvey Amanda J, Harvie Michelle, Hennessy Bryan T, Hiscox Stephen, Holen Ingunn, Howell Sacha J, Howell Anthony, Hubbard Gill, Hulbert-Williams Nick, Hunter Myra S, Jasani Bharat, Jones Louise J, Key Timothy J, Kirwan Cliona C, Kong Anthony, Kunkler Ian H, Langdon Simon P, Leach Martin O, Mann David J, Marshall John F, Martin Lesley, Martin Stewart G, Macdougall Jennifer E, Miles David W, Miller William R, Morris Joanna R, Moss Sue M, Mullan Paul, Natrajan Rachel, O'Connor James P B, O'Connor Rosemary, Palmieri Carlo, Pharoah Paul D P, Rakha Emad A, Reed Elizabeth, Robinson Simon P, Sahai Erik, Saxton John M, Schmid Peter, Smalley Matthew J, Speirs Valerie, Stein Robert, Stingl John, Streuli Charles H, Tutt Andrew N J, Velikova Galina, Walker Rosemary A, Watson Christine J, Williams Kaye J, Young Leonie S, Thompson Alastair M

出版信息

Breast Cancer Res. 2013 Oct 1;15(5):R92. doi: 10.1186/bcr3493.

Abstract

INTRODUCTION

Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.

METHODS

More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.

RESULTS

The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.

CONCLUSIONS

With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

摘要

引言

乳腺癌仍然是一个重大的科学、临床和社会挑战。本差距分析回顾并批判性评估了长期存在的问题以及近期研究中出现的新挑战,并提出了将解决方案转化为实践的策略。

方法

100 多名国际公认的乳腺癌专家科学家、临床医生和医疗保健专业人员合作,探讨九个主题领域:遗传学、表观遗传学和流行病学;分子病理学和细胞生物学;激素影响和内分泌治疗;成像、检测和筛查;当前/新型疗法和生物标志物;耐药性;转移、血管生成、循环肿瘤细胞、癌症“干细胞”;风险与预防;与乳腺癌及其治疗共存和管理。各小组通过反复迭代的过程撰写总结论文,在经过专家和患者的进一步评估后,整合形成了本总结报告。

结果

确定的 10 个主要差距为:(1)了解正常乳腺发育和恶性转化过程中基因和表观遗传变化的功能及背景相互作用;(2)如何实施可持续的生活方式改变(饮食、运动和体重)及化学预防策略;(3)需要定制化的筛查方法,包括具有临床可操作性的检测;(4)增强对乳腺癌亚型、进展和转移背后分子驱动因素的认识;(5)了解肿瘤异质性、休眠、原发或获得性耐药的分子机制,以及如何针对这些动态过程中的关键节点;(6)开发用于化疗敏感性和放射敏感性的经过验证的标志物;(7)了解改善个性化治疗的最佳治疗持续时间、顺序和合理组合;(8)验证多模态成像生物标志物,用于微创诊断和监测原发性和转移性疾病的反应;(9)开发干预措施和支持手段以改善生存体验;(10)持续需要来自正常乳腺、血液、原发性、复发性、转移性和耐药性癌症的临床材料用于转化研究,并获得专业生物信息学支持以最大化其效用。提议的基础设施支持包括增加资源以支持临床相关的体外和体内肿瘤模型;改善获取合适的、经过充分注释的临床样本的途径;扩展生物标志物的发现、验证和标准化;以及促进跨学科合作。

结论

有了资源来开展针对已确定差距的进一步高质量靶向研究,有望在五年内实现知识增长转化为临床护理的改善。

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