&lt;p&gt;Animal models of well-differentiated/dedifferentiated liposarcoma: utility and limitations&lt;/p&gt;

Codenotti, Silvia; Mansoury, Walaa; Pinardi, Luca; Monti, Eugenio; Marampon, Francesco; Fanzani, Alessandro

doi:10.2147/ott.s175710

Cited by 10 publications

(8 citation statements)

References 104 publications

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“…Therapeutic progresses in LPS have been hampered by the disease rarity and the consequent challenge in designing prospective clinical trials and establishing predictive experimental models. In recent years, PDX models of WD/DDLPS, recapitulating tumor histology, biology and genetics, have been developed providing the opportunity to explore novel therapeutic approaches and relevant biomarkers (54,98,119). Patient-derived cell and xenograft models represent valuable tools to assess the therapeutic relevance of molecular alterations that, besides chromosomal amplifications shared by WDLPS and DDLPS, drive liposarcomagenesis and disease progression.…”

Section: Discussionmentioning

confidence: 99%

Beyond targeting amplified MDM2 and CDK4 in well differentiated and dedifferentiated liposarcomas: From promise and clinical applications towards identification of progression drivers

2022

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Well differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS) are tumors of the adipose tissue poorly responsive to conventional cytotoxic chemotherapy which currently remains the standard-of-care. The dismal prognosis of the DDLPS subtype indicates an urgent need to identify new therapeutic targets to improve the patient outcome. The amplification of the two driver genes MDM2 and CDK4, shared by WDLPD and DDLPS, has provided the rationale to explore targeting the encoded ubiquitin-protein ligase and cell cycle regulating kinase as a therapeutic approach. Investigation of the genomic landscape of WD/DDLPS and preclinical studies have revealed additional potential targets such as receptor tyrosine kinases, the cell cycle kinase Aurora A, and the nuclear exporter XPO1. While the therapeutic significance of these targets is being investigated in clinical trials, insights into the molecular characteristics associated with dedifferentiation and progression from WDLPS to DDLPS highlighted additional genetic alterations including fusion transcripts generated by chromosomal rearrangements potentially providing new druggable targets (e.g. NTRK, MAP2K6). Recent years have witnessed the increasing use of patient-derived cell and tumor xenograft models which offer valuable tools to accelerate drug repurposing and combination studies. Implementation of integrated “multi-omics” investigations applied to models recapitulating WD/DDLPS genetics, histologic differentiation and biology, will hopefully lead to a better understanding of molecular alterations driving liposarcomagenesis and DDLPS progression, as well as to the identification of new therapies tailored on tumor histology and molecular profile.

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Section: Discussionmentioning

confidence: 99%

Beyond targeting amplified MDM2 and CDK4 in well differentiated and dedifferentiated liposarcomas: From promise and clinical applications towards identification of progression drivers

2022

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“…Furthermore, inhibition of the pathway and its downstream effector, mTOR, has also been found to induce apoptosis in liposarcoma cell lines [ 93 ]. DDLPS frequently bears additional genetic changes/recurrent mutations as compared to WDLPS, including 1p32 and 6p23 amplifications causing oncogenic overexpression of ASK1/MAP3K5, JUN, and activation of the MAPK pathway [ 10 , 57 , 94 ]. ERK, JNK, and p38 MAP kinase pathway activation have also been observed in transgenic mice with WDLPS development as a downstream response to increased interleukin-22 levels [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics

Tan

He²,

Tang³

et al. 2022

IJMS

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Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests. Recognizing the important role that microRNAs (miRNAs) play in tumorigenesis and their potential utility in tumor classification, we analyzed routine clinical tissue samples of benign and malignant lipomatous tumors, as well as other sarcoma mimics, to identify distinguishing miRNA-based signatures that can aid in the differential diagnosis of these entities. We discovered a 6-miRNA signature that separated lipomas from WDLPS with high confidence (AUC of 0.963), as well as a separate 6-miRNA signature that distinguished DDLPS from their more aggressive histologic mimics (AUC of 0.740). Functional enrichment analysis unveiled possible mechanistic involvement of these predictive miRNAs in adipocytic cancer-related biological processes and pathways such as PI3K/AKT/mTOR and MAPK signaling, further supporting the relevance of these miRNAs as biomarkers for adipocytic tumors. Our results demonstrate that miRNA expression profiling may potentially be used as an adjunctive tool for the diagnosis of benign and malignant adipocytic tumors. Further validation studies are warranted.

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“…A major obstacle hindering cancer research progress is the limited availability of cancer models [13]. Cancer cell lines have been widely used as effective models for drug discovery and preclinical studies.…”

Section: Breast Cancer and Clinical Challengesmentioning

confidence: 99%

Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research

Daneshdoust,

Luo,

et al. 2023

Cells

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Preclinical in vitro models play an important role in studying cancer cell biology and facilitating translational research, especially in the identification of drug targets and drug discovery studies. This is particularly relevant in breast cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (radiotherapy, chemotherapy, immunotherapy, and/or surgery) are relatively lacking. To be clinically relevant, a model must accurately replicate the biology and cellular heterogeneity of the primary tumor. Addressing these requirements and overcoming the limitations of most existing cancer cell lines, which are typically derived from a single clone, we have recently developed conditional reprogramming (CR) technology. The CR technology refers to a co-culture system of primary human normal or tumor cells with irradiated murine fibroblasts in the presence of a Rho-associated kinase inhibitor to allow the primary cells to acquire stem cell properties and the ability to proliferate indefinitely in vitro without any exogenous gene or viral transfection. This innovative approach fulfills many of these needs and offers an alternative that surpasses the deficiencies associated with traditional cancer cell lines. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have applied CR technology to conduct breast cancer research.

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<p>Animal models of well-differentiated/dedifferentiated liposarcoma: utility and limitations</p>

Cited by 10 publications

References 104 publications

Beyond targeting amplified MDM2 and CDK4 in well differentiated and dedifferentiated liposarcomas: From promise and clinical applications towards identification of progression drivers

Beyond targeting amplified MDM2 and CDK4 in well differentiated and dedifferentiated liposarcomas: From promise and clinical applications towards identification of progression drivers

MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics

Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research

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