Voutsadakis Ioannis A
Algoma District Cancer Program, 10066Sault Area Hospital, Sault Ste. Marie, Ontario, Canada, and Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
J Oncol Pharm Pract. 2022 Jun;28(4):945-959. doi: 10.1177/10781552211073673. Epub 2022 Jan 12.
Everolimus is an inhibitor of serine/ threonine kinase mTOR. The drug is approved for the treatment of metastatic ER positive, HER2 negative breast cancers and benefits a subset of patients with these breast cancers in combination with hormonal therapies. Despite extensive efforts, no additional predictive biomarkers to guide therapeutic decisions for everolimus have been introduced in clinical practice.
This paper discusses predictive biomarkers for everolimus efficacy in breast cancer. A search of the medline and web of science databases was performed using the words "everolimus" and "biomarkers". References of retrieved articles were manually scanned for additional relevant articles.
Everolimus benefits a subset of patients with metastatic ER positive, HER2 negative breast cancers in combination with hormonal therapies. Despite extensive efforts no additional predictive biomarkers to guide therapeutic decisions for everolimus therapy have been confirmed for use in clinical practice. However, promising biomarker leads for everolimus efficacy in breast cancer have been suggested and include expression of proteins in the mTOR pathway in ER positive, HER2 negative breast cancers. In HER2 positive cancers mutations, and PTEN expression loss are prognostic. Other clinical predictive biomarkers with more limited data include characteristics derived from whole genome sequencing, subsets of circulating leukocytes and changes in Standardized Uptake Values (SUV) of Positron Emission Tomography (PET) scans.
Putative predictive biomarkers for everolimus efficacy in breast cancer patients, both genomic and clinical, deserve further study and could lead to a better selection of responsive patients.
依维莫司是一种丝氨酸/苏氨酸激酶mTOR的抑制剂。该药物已被批准用于治疗转移性雌激素受体（ER）阳性、人表皮生长因子受体2（HER2）阴性乳腺癌，并且与激素疗法联合使用时可使一部分患有这些乳腺癌的患者受益。尽管进行了大量努力，但在临床实践中尚未引入用于指导依维莫司治疗决策的其他预测性生物标志物。
本文讨论了依维莫司在乳腺癌中疗效的预测性生物标志物。使用“依维莫司”和“生物标志物”等词对医学文献数据库（Medline）和科学网数据库进行了检索。对检索到的文章的参考文献进行了人工筛选以查找其他相关文章。
依维莫司与激素疗法联合使用时，可使一部分转移性ER阳性、HER2阴性乳腺癌患者受益。尽管付出了巨大努力，但尚未确认有其他用于指导依维莫司治疗决策的预测性生物标志物可用于临床实践。然而，已经提出了一些关于依维莫司在乳腺癌中疗效的有前景的生物标志物线索，包括ER阳性、HER2阴性乳腺癌中mTOR途径中蛋白质的表达。在HER2阳性癌症中突变和磷酸酶及张力蛋白同源物（PTEN）表达缺失具有预后意义。其他数据较为有限的临床预测性生物标志物包括全基因组测序衍生的特征、循环白细胞亚群以及正电子发射断层扫描（PET）标准化摄取值（SUV）的变化。
对于乳腺癌患者中依维莫司疗效的假定预测性生物标志物，无论是基因组学还是临床方面的，都值得进一步研究，并且可能有助于更好地选择有反应的患者。
