Potential predictive value of circulating tumor DNA (ctDNA) mutations for the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer

Tan, Qiaorui; Chi, Yunfei; Su, Mu Chun; Zhou, Jinxing; Zhou, Dongdong; Zheng, Fangchao; Man, Xiaochu; Sun, Shujuan; Huang, Jie; Li, Huihui

doi:10.3389/fgene.2023.1125970

Cited by 5 publications

(7 citation statements)

References 79 publications

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“…47,48 Tan et al found that immune checkpoint inhibitors (ICIs) efficacy in patients with advanced triple-negative breast cancer (TNBC) may be predicted by 12 mutant ctDNA genes, including SESN1. 49 Balázs et al found that radiotherapy accentuated the immune suppression of head and neck cancer patients via changing regulatory T cells and CTLA4 and PD-1 expression on CD4 cells in the peripheral blood, and expression of the FXDR, SESN1, GADD45, DDB2, and MDM2 were altered in the peripheral blood cells of patients after radiotherapy. 50 In the present study, KEGG enrichment analysis of the RNA-seq data showed that PD-L1 expression and PD-1 checkpoint pathway in cancer was enriched in the four NB cell lines transfected with SESN1 siRNA #1 and siRNA #2.…”

Section: Discussionmentioning

confidence: 99%

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SESN1 functions as a new tumor suppressor gene via Toll‐like receptor signaling pathway in neuroblastoma

Hua,

Chen,

Gong

et al. 2024

CNS Neurosci Ther

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AimsNeuroblastoma (NB) is the most common extracranial solid tumor in children, with a 5‐year survival rate of <50% in high‐risk patients. MYCN amplification is an important factor that influences the survival rate of high‐risk patients. Our results indicated MYCN regulates the expression of SESN1. Therefore, this study aimed to investigate the role and mechanisms of SESN1 in NB.MethodssiRNAs or overexpression plasmids were used to change MYCN, SESN1, or MyD88's expression. The role of SESN1 in NB cell proliferation, migration, and invasion was elucidated. Xenograft mice models were built to evaluate SESN1's effect in vivo. The correlation between SESN1 expression and clinicopathological data of patients with NB was analyzed. RNA‐Seq was done to explore SESN1's downstream targets.ResultsSESN1 was regulated by MYCN in NB cells. Knockdown SESN1 promoted NB cell proliferation, cell migration, and cell invasion, and overexpressing SESN1 had opposite functions. Knockdown SESN1 promoted tumor growth and shortened tumor‐bearing mice survival time. Low expression of SESN1 had a positive correlation with poor prognosis in patients with NB. RNA‐Seq showed that Toll‐like receptor (TLR) signaling pathway, and PD‐L1 expression and PD‐1 checkpoint pathway in cancer were potential downstream targets of SESN1. Knockdown MyD88 or TLRs inhibitor HCQ reversed the effect of knockdown SESN1 in NB cells. High expression of SESN1 was significantly associated with a higher immune score and indicated an active immune microenvironment for patients with NB.ConclusionsSESN1 functions as a new tumor suppressor gene via TLR signaling pathway in NB.

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Section: Discussionmentioning

confidence: 99%

“…Tan et al. found that immune checkpoint inhibitors (ICIs) efficacy in patients with advanced triple‐negative breast cancer (TNBC) may be predicted by 12 mutant ctDNA genes, including SESN1 49 . Balázs et al.…”

Section: Discussionmentioning

confidence: 99%

SESN1 functions as a new tumor suppressor gene via Toll‐like receptor signaling pathway in neuroblastoma

Hua,

Chen,

Gong

et al. 2024

CNS Neurosci Ther

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“…TILs are mononuclear IC that infiltrate tumor tissue and are present in most types of solid tumors. TILs can be categorized into interstitial (sTIL) and intratumor TILs (iTIL) based on hematoxylin and eosin (H&E) staining ( 55 ). Compared to HR+ and HER2 positive breast cancers, triple-negative breast cancer (TNBC) has a higher level of TILs (20%) ( 56 ).…”

Section: Prognostic and Predictive Value Of Biomarkers Related To Ici...mentioning

confidence: 99%

Narrative review on the role of immunotherapy in early triple negative breast cancer: unveiling opportunities and overcoming challenges

Qian¹,

Liu²

2023

Transl Breast Cancer Res

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Background and Objective Triple negative breast cancer (TNBC) represents a highly aggressive breast cancer subtype, historically managed with chemotherapy regimens predominantly involving anthracyclines and taxanes, yielding unfavorable prognoses. This review endeavors to offer a thorough examination of the present state of treatment strategies for early stage triple negative breast cancer (eTNBC), with a particular emphasis on immunotherapy modalities, combination therapies, predictive biomarkers, and ongoing clinical trials. The principal aim of this review is to meticulously assess the available literature, ascertain significant discoveries, and engage in discussions regarding their potential implications for future research endeavors, clinical applications, and policy formulation. Methods This review was conducted using PubMed and Google Scholar databases, with the latest update performed in March 2023. The search strategy was designed to ensure a comprehensive analysis of the literature, with a focus on recent advancements. Key Content and Findings We critically assess the current eTNBC treatment landscape, covering efficacy and limitations of monotherapy, combination therapies, and predictive biomarkers. We highlight promising results from recent trials, address controversies surrounding chemotherapy, and explore optimal approaches for adjuvant and neoadjuvant therapy (NAT). Insights into personalized treatment strategies, ongoing trials, and future perspectives are provided, advancing our understanding of therapeutic options for eTNBC. Conclusions Through a comprehensive analysis of the literature, this review highlights the potential of immunotherapy, particularly in combination with chemotherapy, as a promising approach for treating eTNBC. However, further research is warranted to optimize treatment strategies, refine patient selection criteria, and identify reliable biomarkers for predicting response to immune checkpoint inhibitors (ICIs). The findings of this review hold significant implications for future research, clinical practice, and policy-making, offering valuable insights into the current challenges and advancements in eTNBC treatment. Ultimately, this knowledge can contribute to improved patient outcomes, enhanced quality of life, and the development of more effective therapeutic approaches for eTNBC.

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“…Tan et al [68] investigated the genomic landscape underlying the response to ICPI treatment. To this end, they performed an Illumina assay of 457 cancer-related genes on plasma samples from 11 ICPI-treated TNBC patients.…”

Section: Ngs Analysis Of Markers For Tnbcmentioning

confidence: 99%

Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications

Tierno

Grassi

Scomersi

et al. 2023

IJMS

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The poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate its potential progression and discover biomarkers related to patient survival. In this review, the NGS applications in TNBC research are described. Many NGS studies point to TP53 mutations, immunocheckpoint response genes, and aberrations in the PIK3CA and DNA repair pathways as recurrent pathogenic alterations in TNBC. Beyond their diagnostic and predictive/prognostic value, these findings suggest potential personalized treatments in PD -L1-positive TNBC or in TNBC with a homologous recombination deficit. Moreover, the comprehensive sequencing of large genomes with NGS has enabled the identification of novel markers with clinical value in TNBC, such as AURKA, MYC, and JARID2 mutations. In addition, NGS investigations to explore ethnicity-specific alterations have pointed to EZH2 overexpression, BRCA1 alterations, and a BRCA2-delaAAGA mutation as possible molecular signatures of African and African American TNBC. Finally, the development of long-read sequencing methods and their combination with optimized short-read techniques promise to improve the efficiency of NGS approaches for future massive clinical use.

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Potential predictive value of circulating tumor DNA (ctDNA) mutations for the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer

Cited by 5 publications

References 79 publications

SESN1 functions as a new tumor suppressor gene via Toll‐like receptor signaling pathway in neuroblastoma

SESN1 functions as a new tumor suppressor gene via Toll‐like receptor signaling pathway in neuroblastoma

Narrative review on the role of immunotherapy in early triple negative breast cancer: unveiling opportunities and overcoming challenges

Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications

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