Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.
Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.
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DOI：
10.1186/bcr3493
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发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Thompson AM
中科院分区：
文献类型：
--
作者：
Eccles SA;Aboagye EO;Ali S;Anderson AS;Armes J;Berditchevski F;Blaydes JP;Brennan K;Brown NJ;Bryant HE;Bundred NJ;Burchell JM;Campbell AM;Carroll JS;Clarke RB;Coles CE;Cook GJ;Cox A;Curtin NJ;Dekker LV;Silva Idos S;Duffy SW;Easton DF;Eccles DM;Edwards DR;Edwards J;Evans D;Fenlon DF;Flanagan JM;Foster C;Gallagher WM;Garcia-Closas M;Gee JM;Gescher AJ;Goh V;Groves AM;Harvey AJ;Harvie M;Hennessy BT;Hiscox S;Holen I;Howell SJ;Howell A;Hubbard G;Hulbert-Williams N;Hunter MS;Jasani B;Jones LJ;Key TJ;Kirwan CC;Kong A;Kunkler IH;Langdon SP;Leach MO;Mann DJ;Marshall JF;Martin L;Martin SG;Macdougall JE;Miles DW;Miller WR;Morris JR;Moss SM;Mullan P;Natrajan R;O'Connor JP;O'Connor R;Palmieri C;Pharoah PD;Rakha EA;Reed E;Robinson SP;Sahai E;Saxton JM;Schmid P;Smalley MJ;Speirs V;Stein R;Stingl J;Streuli CH;Tutt AN;Velikova G;Walker RA;Watson CJ;Williams KJ;Young LS;Thompson AM
乳腺癌仍然是一个重大的科学、临床和社会挑战。该差距分析回顾并批判性地评估了近期研究中出现的持久问题和新挑战，并提出了将解决方案转化为实践的策略。 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解决九个主题领域：遗传学、表观遗传学和流行病学；分子病理学和细胞生物学；荷尔蒙影响和内分泌治疗；成像、检测和筛查；当前/新颖的疗法和生物标志物；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；与乳腺癌共存并进行管理及其治疗。各小组通过迭代过程编写了总结文件，并在专家和患者的进一步评估后，将其合并到这份总结报告中。确定的 10 个主要差距是：（1）了解正常乳房发育和恶性转化过程中遗传和表观遗传变化的功能和背景相互作用； （2）如何实施可持续的生活方式改变（饮食、运动和体重）和化学预防策略； (3) 需要量身定制的筛查方法，包括临床可行的测试； (4) 增强对乳腺癌亚型、进展和转移背后的分子驱动因素的了解； （5）了解肿瘤异质性、休眠、新生或获得性耐药的分子机制以及如何靶向这些动态过程中的关键节点； (6) 开发经过验证的化学敏感性和放射敏感性标记物； (7) 了解治疗的最佳持续时间、顺序和合理组合，以改进个性化治疗； (8) 验证用于微创诊断和监测原发性疾病和转移性疾病反应的多模态成像生物标志物； (9) 制定干预措施和支持以改善生存体验； (10) 持续需要来自正常乳腺癌、血液癌、原发性、复发性、转移性和耐药性癌症的转化研究临床材料，并得到专家生物信息学的支持，以最大限度地发挥其效用。拟议的基础设施推动因素包括增强资源以支持临床相关的体外和体内肿瘤模型；改善对适当、完整注释的临床样本的获取；扩展生物标志物的发现、验证和标准化；并促进跨学科工作。有了资源来开展进一步高质量的有针对性的研究，重点关注已发现的差距，增加的知识转化为改善的临床护理应该可以在五年内实现。
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. 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. 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. 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.
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DOI：
10.1016/s1470-2045(12)70075-x
发表时间：
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期刊：
The Lancet. Oncology
影响因子：
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作者：
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DOI：
10.1038/nrclinonc.2013.42
发表时间：
2013-05
期刊：
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影响因子：
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影响因子：
51.1
作者：
Badve, Sunil;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
影响因子：
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影响因子：
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Andrechek, Eran R.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.