Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences

Priedigkeit, Nolan; Ding, Kai; Horne, William; Kolls, Jay K.; Du, Tian; Lucas, Peter C.; Blohmer, Jens-Uwe; Denkert, Carsten; Machleidt, A; Ingold-Heppner, Barbara; Oesterreich, Steffi; Lee, Adrian V.

doi:10.1186/s13058-020-01379-3

Cited by 29 publications

(18 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, lapatinib inhibited cell viability in samples of primary and metastatic neoplasms even with low or negative HER2 expression. This action is also observed in humans and makes lapatinib an excellent therapeutic option in the treatment of metastatic breast neoplasms [ 48 , 49 ]. Therefore, lapatinib is a possible alternative that should be studied for the treatment of dogs with metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

“…Although our study focused on HER2+ neoplasms, lapatinib has also been studied as a possible therapeutic alternative for triple-negative breast neoplasms, which generally show increased EGFR expression [ 47 , 48 , 50 ]. Studies on this subtype have demonstrated the ability of lapatinib, when combined with other drugs, to inhibit the migration of triple-negative human breast cancer cells [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies on this subtype have demonstrated the ability of lapatinib, when combined with other drugs, to inhibit the migration of triple-negative human breast cancer cells [ 47 ]. In addition, in a study of human patients with metastatic triple-negative breast cancer treated with lapatinib and veliparib, 35% (6/17) of the patients responded to the therapy, with less than 10% of the patients having adverse effects, all of which were moderate [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Lapatinib on HER2-Positive and HER2-Negative Canine Mammary Carcinoma Cells Cultured In Vitro

et al. 2021

View full text Add to dashboard Cite

HER2 is a prognostic and predictive marker widely used in breast cancer. Lapatinib is a tyrosine kinase inhibitor that works by blocking the phosphorylation of the receptor HER2. Its use is related to relatively good results in the treatment of women with HER2+ breast cancer. Thus, this study aimed to verify the effects of lapatinib on four canine primary mammary gland carcinoma cell cultures and two paired metastatic cell cultures. Cultures were treated with lapatinib at concentrations of 100, 500, 1000 and 3000 nM for 24 h and the 50% inhibitory concentration (IC50) for each cell culture was determined. In addition, a transwell assay was performed to assess the ability of lapatinib to inhibit cell migration. Furthermore, we verified HER2 expression by RT-qPCR analysis of cell cultures and formalin-fixed paraffin-embedded tissues from samples corresponding to those used in cell culture. Lapatinib was able to inhibit cell proliferation in all cell cultures, but it was not able to inhibit migration in all cell cultures. The higher the expression of HER2 in a culture, the more sensitive the culture was to treatment. This relationship may be an indication that the expression of HER2 may be a predictive factor and opens a new perspective for the treatment of primary and metastatic mammary gland cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Lapatinib on HER2-Positive and HER2-Negative Canine Mammary Carcinoma Cells Cultured In Vitro

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Besides, those patients with ≥5 CTC develop resistance earlier. RB expression was also analysed but there was no correlation with clinical benefit [ 55 ]. Although this is the first study reported based on CTCs enumeration or molecular analysis in these patients, a bigger cohort and more analysis are required, as CTC characterisation will increase their clinical utility.…”

Section: Circulating Tumour Cell (Ctc) Analysis As a Novel Biomarker For Managing Hr+/her2− Mbc Patientsmentioning

confidence: 99%

Liquid Biopsy: A New Tool for Overcoming CDKi Resistance Mechanisms in Luminal Metastatic Breast Cancer

González-Conde

Yáñez-Gómez

López‐López

et al. 2021

JPM

View full text Add to dashboard Cite

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2− BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi), in combination with an aromatase inhibitor or fulvestrant, have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2− metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all of the patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms that underlie this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease, and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We mainly focus on those studies that describe the possible resistance mechanisms in circulating tumour-derived material.

show abstract

“… 11 Moreover, BRD1 has been associated with nodular prostate diseases and schizophrenia BRD1 also shows single-nucleotide variant enrichment in estrogen-deprived breast cancer. 12 …”

Section: Introductionmentioning

confidence: 99%

Expression Characteristics and Clinical Correlations of BRD1 in Colorectal Cancer Samples

Zhou

Wang

et al. 2021

Technol Cancer Res Treat

View full text Add to dashboard Cite

The incidence of colorectal cancer (CRC), as well as subsequent patient mortality, has increased in the last decade; an unhealthy diet is considered to be the leading cause. Previous studies have shown the potential of the bromodomain containing 1 ( BRD1) gene as a therapeutic target for CRC based on its specificity; however, the genetic mode of action and expression in CRC cells are yet to be investigated. In this study, target genes were screened from single-cell transcriptome sequencing data, and the collected clinical specimens were subjected to immunohistochemistry (IHC) to identify the protein expression of target genes; the results were verified in the GSE17536 array set. Receiver operating characteristic curves (ROC) and overall survival (OS) were used to test target genes as biomarkers and independent predictive markers for CRC. Based on these results, BRD1 was screened as a target gene, and IHC results showed that BRD1 protein expression in CRC was higher than that in normal tissues and was significantly upregulated in poorly differentiated (PD) CRC. ROC analysis showed that the area under the curve in the collected clinical specimens and GSE17536 were 0.6062 and 0.6094, respectively. OS analysis showed that higher BRD1 protein expression was associated with a significantly shorter survival time. In conclusion, BRD1 expression was positively correlated with PD CRC and negatively correlated with OS, indicating that BRD1 could predict the differentiation state of CRC and may be a novel predictive biomarker.

show abstract

Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences

Cited by 29 publications

References 79 publications

Effects of Lapatinib on HER2-Positive and HER2-Negative Canine Mammary Carcinoma Cells Cultured In Vitro

Effects of Lapatinib on HER2-Positive and HER2-Negative Canine Mammary Carcinoma Cells Cultured In Vitro

Liquid Biopsy: A New Tool for Overcoming CDKi Resistance Mechanisms in Luminal Metastatic Breast Cancer

Expression Characteristics and Clinical Correlations of BRD1 in Colorectal Cancer Samples

Contact Info

Product

Resources

About