ArticleBreast cancer research and treatment2021
Concurrent mutations associated with trastuzumab-resistance revealed by single cell sequencing.
Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06125834 (Trastuzumab Emtansine), which is not on this map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Trastuzumab Emtansine (T-DM1) Treatment in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy: a Multicenter, Single-arm, Phase II Study
Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Decoding the Collagenome in Breast Cancer: Mechanotransduction, Microenvironment, and Translational Opportunities.International journal of molecular sciences · 2026Review
- Single-Cell RNA-Sequencing: Opening New Horizons for Breast Cancer Research.International journal of molecular sciences · 2024Review
- JMJD6 functions as an oncogene and is associated with poor prognosis in esophageal squamous cell carcinoma.BMC cancer · 2023Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeHER2-positive breast cancer patients benefit from HER2-targeted therapies, among which the most commonly used is trastuzumab. However, acquired resistance typically happens within one year. The cellular heterogeneity of it is less clear.
methodsHere we generated trastuzumab-resistant cells in two HER2-positive breast cancer cell lines, SK-BR-3 and BT-474. Cells at different time points during the resistance induction were examined by exome sequencing to study changes of genomic alterations over time. Single cell-targeted sequencing was also used to identify resistance-associated concurrent mutations.
resultsWe found a rapid increase of copy number variation (CNV) regions and gradual accumulation of single nucleotide variations (SNVs). On the pathway level, non-synonymous SNVs for SK-BR-3 cells were enriched in the MAPK signaling pathway, while for BT-474 cells they were enriched in mTOR and PI3K-Akt signaling pathways. However, all of the three signaling pathways were in the downstream of the HER2 kinase. Putative trastuzumab-resistance-associated SNVs included AIFM1 P548L and ERBB2 M833R in SK-BR-3 cells, and ADAMTS19 V451L, OR5M9 D230N, COL9A1 R627T, and ITGA7 H911Q in BT-474 cells. Single-cell-targeted sequencing identified several concurrent mutations. By validation, we found that concurrent mutations (AIFM1 P548L and IL1RAPL2 S546C in SK-BR-3 cells, MFSD11 L242I and ANAPC4 E16K in BT-474 cells) led to a decrease of trastuzumab sensitivity.
conclusionTaken together, our study revealed a common pathway level trastuzumab-resistance mechanism for HER2-positive breast cancer cells. In addition, our identification of concurrent SNVs associated with trastuzumab-resistance may be indicative of potential targets for the treatment of trastuzumab-resistant breast cancer patients.
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