Stravodimou Athina, Voutsadakis Ioannis A
Department of Medical Oncology, CHUV, Lausanne 1011, Switzerland.
Department of Medical Oncology, Sault Area Hospital, Sault Ste Marie P6B0A8, Ontario, Canada.
World J Clin Oncol. 2022 Feb 24;13(2):135-146. doi: 10.5306/wjco.v13.i2.135.
Breast cancer is the most common female cancer and a major cause of morbidity and mortality. Progress in breast cancer therapeutics has been attained with the introduction of targeted therapies for specific sub-sets. However, other subsets lack targeted interventions and thus there is persisting need for identification and characterization of molecular targets in order to advance breast cancer therapeutics.
To analyze the role of lesions in neurotrophic receptor tyrosine kinase (NTRK) genes in breast cancers.
Analysis of publicly available genomic breast cancer datasets was performed for identification and characterization of cases with fusions and other molecular abnormalities involving , and genes.
NTRK fusions are present in a small number of breast cancers at the extensive GENIE project data set which contains more than 10000 breast cancers. These cases are not identified as secretory in the database, suggesting that the histologic characterization is not always evident. In the breast cancer The Cancer Genome Atlas (TCGA) cohort the more common molecular lesion in NTRK genes is amplification of observed in 7.9% of breast cancers.
Neurotrophin receptors molecular lesions other than fusions are observed more often than fusions. However, currently available NTRK inhibitors are effective mainly for fusion lesions. Amplifications of , being more frequent in breast cancers, could be a viable therapeutic target if inhibitors efficacious for them become available.
乳腺癌是最常见的女性癌症,也是发病和死亡的主要原因。随着针对特定亚组的靶向治疗的引入,乳腺癌治疗取得了进展。然而,其他亚组缺乏靶向干预措施,因此仍然需要鉴定和表征分子靶点以推进乳腺癌治疗。
分析神经营养受体酪氨酸激酶(NTRK)基因病变在乳腺癌中的作用。
对公开可用的基因组乳腺癌数据集进行分析,以鉴定和表征涉及NTRK1、NTRK2和NTRK3基因融合及其他分子异常的病例。
在包含超过10000例乳腺癌的广泛GENIE项目数据集中,少数乳腺癌存在NTRK融合。这些病例在数据库中未被鉴定为分泌性癌,这表明组织学特征并不总是明显的。在乳腺癌癌症基因组图谱(TCGA)队列中,NTRK基因中较常见的分子病变是NTRK3扩增,在7.9%的乳腺癌中观察到。
除融合外,神经营养因子受体分子病变比融合更常见。然而,目前可用的NTRK抑制剂主要对融合病变有效。NTRK3扩增在乳腺癌中更频繁,如果有对其有效的抑制剂,可能成为一个可行的治疗靶点。