Applications of Circulating Tumor Cells and Circulating Tumor DNA in Precision Oncology for Breast Cancers

Addanki, Sridevi; Meas, Salyna; Sarli, Vanessa N.; Singh, Balraj; Lucci, Anthony

doi:10.3390/ijms23147843

Cited by 27 publications

(10 citation statements)

References 113 publications

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“…Some studies have highlighted potential benefits of the measurement of cell-free DNA fragments (cfDNA), which are released from the tumour and healthy cells into the bloodstream as a result of apoptosis, necrosis, NETosis, and active secretion via extracellular vesicles [9,[12][13][14][15][16]. According to the American Society of Clinical Oncology and the College of American Pathologists, the largest fraction of cfDNA in patients with cancer is derived from the tumour tissue of origin [17].…”

Section: Of 13mentioning

confidence: 99%

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

Jarmuzek,

Wawrzyniak-Gramacka,

Morawin

et al. 2024

IJMS

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Novel blood-circulating molecules, as potential biomarkers for glioblastoma multiforme (GBM) diagnosis and monitoring, are attracting particular attention due to limitations of imaging modalities and invasive tissue biopsy procedures. This study aims to assess the diagnostic and prognostic values of circulating cell-free DNA (cfDNA) in relation to inflammatory status in GBM patients and to determine the concentration and average size of DNA fragments typical of tumour-derived DNA fractions. Preoperative plasma samples from 40 patients (GBM 65.0 ± 11.3 years) and 40 healthy controls (HC 70.4 ± 5.4 years) were compared. The cfDNA concentrations and lengths were measured using the electrophoresis platform, and inflammatory indices (NLR, PLR, LMR, and SII) were calculated from complete blood cell analysis. More fragmented cfDNA and 4-fold higher 50–700 bp cfDNA concentrations were detected in GBM patients than in healthy controls. The average cfDNA size in the GBM group was significantly longer (median 336 bp) than in the HC group (median 271 bp). Optimal threshold values were 1265 pg/μL for 50–700 bp cfDNA (AUC = 0.857) and 290 bp for average cfDNA size (AUC = 0.814). A Kaplan–Meier survival curves analysis also demonstrated a higher mortality risk in the GBM group with a cut-off >303 bp cfDNA. This study is the first to have revealed glioblastoma association with high levels of cfDNA > 1000 pg/μL of 50–700 bp in length, which can be aggravated by immunoinflammatory reactivity.

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Section: Of 13mentioning

confidence: 99%

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

Jarmuzek,

Wawrzyniak-Gramacka,

Morawin

et al. 2024

IJMS

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“…Besides, the detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in liquid biopsy has been investigated as a way to assess anti-HER2 therapy response and explain resistance. In fact, the presence of CTCs and ctDNA before and after treatment is associated with a worse prognosis and increased likelihood of developing resistance to anti-HER2 therapy [ 71 ].…”

Section: Future Directionsmentioning

confidence: 99%

Clinical Impact of New Treatment Strategies for HER2-Positive Metastatic Breast Cancer Patients with Resistance to Classical Anti-HER Therapies

Tapia,

Hernando,

Martínez

et al. 2023

Cancers

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HER2-positive breast cancer accounts for 15–20% of all breast cancer cases. This subtype is characterized by an aggressive behavior and poor prognosis. Anti-HER2 therapies have considerably improved the natural course of the disease. Despite this, relapse still occurs in around 20% of patients due to primary or acquired treatment resistance, and metastasis remains an incurable disease. This article reviews the main mechanisms underlying resistance to anti-HER2 treatments, focusing on newer HER2-targeted therapies. The progress in anti-HER2 drugs includes the development of novel antibody–drug conjugates with improvements in the conjugation process and novel linkers and payloads. Moreover, trastuzumab deruxtecan has enhanced the efficacy of trastuzumab emtansine, and the new drug trastuzumab duocarmazine is currently undergoing clinical trials to assess its effect. The combination of anti-HER2 agents with other drugs is also being evaluated. The addition of immunotherapy checkpoint inhibitors shows some benefit in a subset of patients, indicating the need for useful biomarkers to properly stratify patients. Besides, CDK4/6 and tyrosine kinase inhibitors are also included in the design of new treatment strategies. Lapitinib, neratinib and tucatinib have been approved for HER2-positive metastasis patients, however clinical trials are currently ongoing to optimize combined strategies, to reduce toxicity, and to better define the useful setting. Clinical research should be strengthened along with the discovery and validation of new biomarkers, as well as a deeper understanding of drug resistance and action mechanisms.

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“…It detects peripheral CTCs and provides information regarding the tumor and the patient’s prognosis in conjunction with clinical outcomes. CTCs can monitor residual disease, assess treatment response, and track disease progression and tumor evolution, including developing resistance to therapy [ 10 ]. Their distinctive features are associated with patients’ overall survival and progression-free survival [ 2 ].…”

Section: Circulating Tumor Cells: Overviewmentioning

confidence: 99%

Targeting circulating tumor cells to prevent metastases

Gostomczyk,

Marsool,

Tayyab

et al. 2023

Human Cell

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Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor, enter the bloodstream or body fluids, and spread to other body parts, leading to metastasis. Their presence and characteristics have been linked to cancer progression and poor prognosis in different types of cancer. Analyzing CTCs can offer valuable information about tumors’ genetic and molecular diversity, which is crucial for personalized therapy. Epithelial-mesenchymal transition (EMT) and the reverse process, mesenchymal-epithelial transition (MET), play a significant role in generating and disseminating CTCs. Certain proteins, such as EpCAM, vimentin, CD44, and TGM2, are vital in regulating EMT and MET and could be potential targets for therapies to prevent metastasis and serve as detection markers. Several devices, methods, and protocols have been developed for detecting CTCs with various applications. CTCs interact with different components of the tumor microenvironment. The interactions between CTCs and tumor-associated macrophages promote local inflammation and allow the cancer cells to evade the immune system, facilitating their attachment and invasion of distant metastatic sites. Consequently, targeting and eliminating CTCs hold promise in preventing metastasis and improving patient outcomes. Various approaches are being explored to reduce the volume of CTCs. By investigating and discussing targeted therapies, new insights can be gained into their potential effectiveness in inhibiting the spread of CTCs and thereby reducing metastasis. The development of such treatments offers great potential for enhancing patient outcomes and halting disease progression.

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Applications of Circulating Tumor Cells and Circulating Tumor DNA in Precision Oncology for Breast Cancers

Cited by 27 publications

References 113 publications

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

Clinical Impact of New Treatment Strategies for HER2-Positive Metastatic Breast Cancer Patients with Resistance to Classical Anti-HER Therapies

Targeting circulating tumor cells to prevent metastases

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