PIK3CA copy-number gain and inhibitors of the PI3K/AKT/mTOR pathway in triple-negative breast cancer.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Ottavia Amato, Laurence Buisseret, Geraldine Gebhart, Nicolas Plouznikoff, Denis Larsimont, Ahmad Awada, Martine Piccart, Philippe Aftimos
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引用次数: 1

Abstract

As wider insights are gained on the molecular landscape of triple-negative breast cancer (TNBC), novel targeted therapeutic strategies might become an option in this setting as well. Activating mutations of PIK3CA represent the second most common alteration in TNBC after the TP53 mutation, with a prevalence of ∼10%-15%. Considering the well-established predictive role of PIK3CA mutations for response to agents targeting the PI3K/AKT/mTOR pathway, several clinical trials are currently evaluating these drugs in patients with advanced TNBC. However, much less is known regarding the actionability of PIK3CA copy-number gains, which represent a thoroughly common molecular alteration in TNBC, with a prevalence estimated at 6%-20%, and are listed as "likely gain-of-function" alterations in the OncoKB database. In the present paper, we describe two clinical cases in which patients harboring PIK3CA-amplified TNBC received a targeted treatment with the mTOR-inhibitor everolimus and the PI3K-inhibitor alpelisib, respectively, with evidence of disease response on 18F-FDG positron-emission tomography (PET) imaging. Hence, we discuss the evidence presently available regarding a possible predictive value of PIK3CA amplification for response to targeted treatment strategies, suggesting that this molecular alteration might represent an intriguing biomarker in this sense. Considering that few of the currently active clinical trials assessing agents targeting the PI3K/AKT/mTOR pathway in TNBC select patients based on tumor molecular characterization, and none of these based on PIK3CA copy-number status, we urge for the introduction of PIK3CA amplification as a criterion for patient selection in future clinical trials in this setting.

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三阴性乳腺癌中PIK3CA拷贝数增益和PI3K/AKT/mTOR通路抑制剂
随着对三阴性乳腺癌(TNBC)分子景观的更广泛了解,新的靶向治疗策略也可能成为这种情况下的一种选择。PIK3CA的激活突变是TNBC中仅次于TP53突变的第二大常见突变,患病率约为10%-15%。考虑到PIK3CA突变对靶向PI3K/AKT/mTOR通路的药物反应的预测作用,目前有几项临床试验正在评估这些药物在晚期TNBC患者中的作用。然而,对于PIK3CA拷贝数增益的可操作性知之甚少,PIK3CA拷贝数增益代表TNBC中完全常见的分子改变,患病率估计为6%-20%,并且在OncoKB数据库中被列为“可能的功能增益”改变。在本文中,我们描述了两个临床病例,其中携带pik3ca扩增的TNBC患者分别接受了mtor抑制剂依维莫司和pi3k抑制剂alpelisib的靶向治疗,并在18F-FDG正电子发射断层扫描(PET)成像中有疾病反应的证据。因此,我们讨论了目前可用的关于PIK3CA扩增对靶向治疗策略反应的可能预测价值的证据,表明这种分子改变可能在这个意义上代表了一个有趣的生物标志物。考虑到目前正在进行的评估TNBC中靶向PI3K/AKT/mTOR通路的药物的临床试验中,很少根据肿瘤分子特征选择患者,而这些试验都没有基于PIK3CA拷贝数状态,我们敦促在未来的临床试验中引入PIK3CA扩增作为患者选择的标准。
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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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