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

ABSTRACT: Breast cancer is the most common cancer in women worldwide. The heterogeneity of breast cancer and drug resistance to therapies make the diagnosis and treatment difficult. Molecular imaging methods with positron emission tomography (PET) and single-photon emission tomography (SPECT) provide useful tools to diagnose, predict, and monitor the response of therapy, contributing to precision medicine for breast cancer patients. Recently, many efforts have been made to find new targets for breast cancer therapy to overcome resistance to standard of care treatments, giving rise to new therapeutic agents to offer more options for patients with breast cancer. The combination of diagnostic and therapeutic strategies forms the foundation of theranostics. Some of these theranostic agents exhibit high potential to be translated to clinic. In this review, we highlight the most recent advances in theranostics of the different molecular subtypes of breast cancer in preclinical studies.

SUBMITTER: Fang H

PROVIDER: S-EPMC8111013 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Fang Hanyi H Cavaliere Alessandra A Li Ziqi Z Huang Yiyun Y Marquez-Nostra Bernadette B

Frontiers in pharmacology 20210427

Breast cancer is the most common cancer in women worldwide. The heterogeneity of breast cancer and drug resistance to therapies make the diagnosis and treatment difficult. Molecular imaging methods with positron emission tomography (PET) and single-photon emission tomography (SPECT) provide useful tools to diagnose, predict, and monitor the response of therapy, contributing to precision medicine for breast cancer patients. Recently, many efforts have been made to find new targets for breast canc ...[more]

PMID: 33986665

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Project description:Colorectal cancer (CRC) is a heterogeneous disease. More insight into the biological diversity of CRC is needed to improve therapeutic outcomes. Established CRC cell lines are frequently used and were shown to be representative models of the main subtypes of CRC at the genomic and transcriptomic level. In the present work, we established stable, luciferase expressing derivatives from 10 well-established CRC cell lines, generated spheroids and subcutaneous xenograft tumors in nude mice, and performed comparative characterization of these model systems. Transcriptomic analyses revealed the close relation of cell lines with their derived spheroids and xenograft tumors. The preclinical model systems clustered with patient tumor samples when compared to normal tissue thereby confirming that cell-line-based tumor models retain specific characteristics of primary tumors. Xenografts showed different differentiation patterns and bioluminescence imaging revealed metastatic spread to the lungs. In addition, the models were classified according to the CMS classification system, with further sub-classification according to the recently identified two intrinsic epithelial tumor cell states of CRC, iCMS2 and iCMS3. The combined data showed that regarding primary tumor characteristics, 3D-spheroid cultures resemble xenografts more closely than 2D-cultured cells do. Furthermore, we set up a bioluminescence-based spheroid cytotoxicity assay in order to be able to perform dose-response relationship studies in analogy to typical monolayer assays. Applying the established assay, we studied the efficacy of oxaliplatin. Seven of the ten used cell lines showed a significant reduction in the response to oxaliplatin in the 3D-spheroid model compared to the 2D-monolayer model. Therapy studies in selected xenograft models confirmed the response or lack of response to oxaliplatin treatment. Analyses of differentially expressed genes in these models identified CAV1 as a possible marker of oxaliplatin resistance. In conclusion, we established a combined 2D/3D, in vitro/in vivo model system representing the heterogeneity of CRC, which can be used in preclinical research applications.

Project description:BackgroundAlthough the conversion of clinically used breast cancer biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) between primary tumors and metastatic lesions is well recognized, data on whether receptor conversion has an effect on therapy management and survival in patients with metastatic breast cancer is limited. This study aimed to investigate the clinical implications of receptor conversion throughout tumor progression.MethodsIn total, 2450 patients diagnosed with metastatic breast cancer in Tianjin Medical University Cancer Institute and Hospital were analyzed and 426 female patients with available biopsy results from both primary and metastatic sites were included in this study. We investigated the alteration of ER, PR and HER2 during breast cancer progression and evaluated the therapy management and prognostic value of receptor conversion.ResultsThe conversion rates of ER, PR, and HER2 between primary tumors and metastasis were 21.1% (McNemar's test p < 0.001), 33.2% (p < 0.001), and 11.6% (p = 0.868), respectively. Evaluation of ER, PR, and HER2 status in multiple consecutive metastases revealed a change in 19.1% (p > 0.05), 23.5% (p = 0.021), and 9.8% (p > 0.05) of patients, respectively. Adjuvant therapy (chemotherapy/endocrine therapy) was related to hormone receptor conversion (p < 0.05). A statistically significant differential survival associated with hormone receptor (ER/PR) conversion (log-rank p < 0.05) was observed. In the multivariate analysis, ER conversion was an independent influence factor of survival (p < 0.05). Molecular typing conversion in primary and metastatic lesions also had a significant effect on survival (p < 0.05). We found that changing treatment based on the receptor conversion could affect clinical outcomes (p < 0.05).ConclusionsOur findings indicated that receptor conversion during breast tumor progression had a significant effect on survival. Most importantly, our findings proved that patients with receptor conversion benefited from a change in therapy.

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

Publications

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

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