Preclinical Advances in Theranostics for the Different Molecular Subtypes of Breast Cancer

Fang, Hanyi; Cavaliere, Alessandra; Li, Ziqi; Huang, Yiyun; Marquez-Nostra, Bernadette

doi:10.3389/fphar.2021.627693

Cited by 10 publications

(7 citation statements)

References 169 publications

(213 reference statements)

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“…Yet, the vast numbers of BC cases are not linked to a higher penetrance mutated gene, but to genes of lower penetrance such as BRIP1 which are often mutated in the general population. 18,19 The BRIP1 gene is morphologically expressed in both malignant and healthy cells. BRIP1 interacts with numerous proteins associated with regulation of DNA damage responses and checkpoint signaling, which are vital for retaining chromosomal and genomic constancy.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Value Estimation of BRIP1 in Breast Cancer by Exploiting Transcriptomics Data Through Bioinformatics Approaches

Khan

2021

Bioinform Biol Insights

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BRIP1 (Breast Cancer 1 Interacting Helicase 1) is a tumor suppressor gene that has vital function in preserving the genetic stability by repairing DNA damage though have significant associations with the onset of breast cancer (BC) if mutated or overexpressed. In this study, the prognostic value of BRIP1 gene was evaluated and validated through bioinformatics approaches utilizing transcriptomic (mRNA expression) data from several BC databases. To determine the prognostic value, the expression level of mRNA transcript was analyzed in context of comparison between breast tumor and normal tissues regarding clinical features, breast tumor subtypes, promoter methylation status, correlation level, mutation frequency, and survival of BC patients. BRIP1 expression was found to be significantly overexpressed in various BC molecular subtypes (e.g. PAM50, Sorlie’s) and clinical status (estrogen and progesterone receptor) than associated normal tissues which correlated with prognosis. Also, in promoter methylation level, its expression was observed as upregulated-hypomethylated regarding various clinicopathological features. Multiple data mining exhibited positive correlation between BRIP1 and INTS2 (Integrator Complex Subunit 2) expressions in BC. Further, mutation analysis revealed that BRIP1 gene was altered by acquiring both somatic and germline mutations. In addition, a total of 42 mutations; 24 missense, 8 fusion, 7 truncating, and 3 inframe mutations in BC patients was detected in BRIP1 protein. Moreover, higher BRIP1 expression was found to be correlated with poor disease-specific, disease metastasis-free, relapse-free, and overall survivals of BC patients. Since, overexpression of BRIP1 was identified to be associated with different clinical features, breast tumor subtypes, promoter methylation status, and survival of BC patients that may provide a risk of ensuing malignant transformation. Thus, lower expression of BRIP1 might hinder BC prognosis. We consider that this analysis will present a proof for BRIP1 gene to be a noteworthy molecular biomarker for BC prognosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Value Estimation of BRIP1 in Breast Cancer by Exploiting Transcriptomics Data Through Bioinformatics Approaches

Khan

2021

Bioinform Biol Insights

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“…Breast cancer is an evolutionary heterogeneous tumour, and its molecular subtype can convert between bone metastatic lesions and primary tumors [ 11 , 12 ]. Therefore, it is significant that early detection of BM and personalized treatment based on molecular subtypes, which can preserve or improve long-term quality of life and functional independence of BC patients with BM [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Is it sufficient to evaluate metastatic bone involvement in breast cancer using SPECT/CT? A new approach of SPECT/CT-guided targeted bone marrow biopsy

Chen

Zhang

2022

BMC Cancer

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Objective To investigate the feasibility, safety, and clinical application value of single photon emission computed tomography/computed tomography (SPECT/CT)-guided bone marrow biopsy (BMB) in breast cancer (BC) patients with suspected bone metastases (BM) and compare its diagnostic performance for detection of BM with SPECT/CT. Methods The records of breast cancer patients referred for bone scintigraphy (BS), SPECT/CT and SPECT/CT-guided BMB from January of 2018 to June of 2021 in our hospital were retrospectively reviewed. 49 Patients were consecutively included in this study, all 49 specimens were analyzed by pathological and immunohistochemical studies.The biopsy success rate, total examination time, biopsy operation time, complications, CT radiation dose, and pathological and immunohistochemical results were recorded. The diagnostic performance based on SPECT/CT and SPECT/CT-guided BMB were compared with pathological, immunohistochemical examinations and the results of subsequent follow-up. Results Bone samples of the sites with high uptake were obtained in all 49 patients under BMB. No severe postoperative complications occurred. Among all 49 cases, 34 specimens were positive for metastatic breast cancer (69%, 34/49), and positive for benign tissue in 15 cases (31%, 15/49). 1 case of 15 cases was subsequently diagnosed as metastatic breast cancer according to the follow-up result. SPECT/CT-guided BMB demonstrated significantly higher negative predictive value (NPV) when compared to SPECT/CT (p = 0.021 < 0.05). Patients with differential expression of ER, PR, and HER-2 between primary lesions and metastatic lesions accounted for 12, 17, and 5 cases, respectively, and the changing rates were 35.2% (12/34), 50% (17/34), and 14.7% (5/34), respectively. Molecular subtype changes occurred in 7 patients, accounting for 47% (16/34) of metastatic patients. Conclusion It is insufficient to evaluate BM in BC patients using SPECT/CT imaging. SPECT/CT-guided BMB provided significantly higher sensitivity and NPV than SPECT/CT for detection of BM in BC patients. Our research redefines a new approach which can confirm diagnosis and potential molecular subtype changes for suspected bone metastatic lesions in BC patients, which can offer important opportunities for precision treatment and improved quality of life of BC patients with BM.

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“…The potential for receptor-targeted imaging represents an attractive and promising aspect of nanotheranostics. Several receptor-targeted imaging modalities have been employed previously in the theranostic imaging of some cancers. , These modalities include imaging strategies, including optical imaging, , nuclear imaging, ultrasound imaging, and magnetic resonance imaging (MRI) imaging . Of these, receptor-targeted fluorescence imaging has emerged as the principal strategy for the diagnosis of different cancers, including breast cancer, glioma, lung cancer, ovarian cancer, and melanoma …”

Section: Introductionmentioning

confidence: 99%

Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models

Johnson

Kopecky

Koshy

et al. 2023

ACS Biomater. Sci. Eng.

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The time interval between the diagnosis of tumor in a patient and the initiation of treatment plays a key role in determining the survival rates. Consequently, theranostics, which is a combination of diagnosis and treatment, can be expected to improve survival rates. Early detection and immediate treatment initiation are particularly important in the management of melanoma, where survival rates decrease considerably after metastasis. The present work reports for the first time the application of fluorescein isothiocyanate (FITC)tagged epidermal growth factor receptor (EGFR)-functionalized ceria nanoparticles, which exhibit intrinsic reactive oxygen species (ROS)mediated anticancer effects, for the EGFR-targeted diagnosis and treatment of melanoma. The theranostic activity was demonstrated using two-dimensional (2D) and three-dimensional (3D) models of parental and metastatic melanoma. Confocal imaging studies confirm the diagnostic activity of the system. The therapeutic efficiency was evaluated using cell viability studies and ROS measurements. The ROS elevation levels are compared across the 2D and 3D models. Significant enhancement in the generation of cellular ROS and absence in mitochondrial ROS are observed in the 2D models. In contrast, significant elevations in both ROS types are observed for the 3D models, which are significantly higher for the metastatic spheroids than the parental spheroids, thus indicating the suitability of this nanoformulation for the treatment of metastatic melanoma.

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Preclinical Advances in Theranostics for the Different Molecular Subtypes of Breast Cancer

Cited by 10 publications

References 169 publications

Prognostic Value Estimation of BRIP1 in Breast Cancer by Exploiting Transcriptomics Data Through Bioinformatics Approaches

Prognostic Value Estimation of BRIP1 in Breast Cancer by Exploiting Transcriptomics Data Through Bioinformatics Approaches

Is it sufficient to evaluate metastatic bone involvement in breast cancer using SPECT/CT? A new approach of SPECT/CT-guided targeted bone marrow biopsy

Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models

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