Liposarcoma: molecular targets and therapeutic implications

Bill, Kate Lynn J.; Casadei, Lucia; Prudner, Bethany C.; Iwenofu, Hans; Strohecker, Anne M.; Pollock, Raphael E.

doi:10.1007/s00018-016-2266-2

Cited by 38 publications

(44 citation statements)

References 67 publications

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“…Human liposarcoma (LPS) is the most common soft-tissue sarcoma subtype, comprising 24–45% of all such forms of malignancy (1). LPS is classified into four subtypes: 1) well-differentiated (WDLPS), 2) de-differentiated (DDLPS), 3) myxoid/round cell LPS (MRC) and 4) pleomorphic LPS (1).…”

Section: Introductionmentioning

confidence: 99%

“…LPS is classified into four subtypes: 1) well-differentiated (WDLPS), 2) de-differentiated (DDLPS), 3) myxoid/round cell LPS (MRC) and 4) pleomorphic LPS (1). WDLPS and DDLPS are characterized by chromosomal amplification at 12q13-q22, which contains the MDM2 and CDK4 genes (90% of the cases).…”

Section: Introductionmentioning

confidence: 99%

“…Surgical resection with negative margins remains the mainstay of definitive treatment for operable disease. However, high rates of local recurrence, coupled with acquisition of metastatic capacity in DDLPS (but not WDLPS), points to the need for even earlier therapeutic intervention than is currently possible due to limitations in detections of recurrence (1). …”

Section: Introductionmentioning

confidence: 99%

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Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression

Casadei

Calore

Creighton³

et al. 2017

Cancer Research

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149

116

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Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25–3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25–3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Precis: Two extracellular vesicle-derived microRNAs are found to drive liposarcoma progression by stimulating the secretion of pro-inflammatory IL-6 from tumor-associated macrophages, offering new theranostic opportunities in this cancer setting.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression

Casadei

Calore

Creighton³

et al. 2017

Cancer Research

Self Cite

149

116

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“…Prognosis typically remains poor, with variable but high recurrence rates. Distinct molecular mechanisms are involved in the pathogenesis of each subtype, which may allow identification of more precise and successful targeted therapeutics …”

Section: Introductionmentioning

confidence: 99%

Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate‐grade or high‐grade liposarcoma

Samuels¹,

Chawla

Somaiah

et al. 2017

Cancer

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“…Additionally, nelfinavir, a protease inhibitor used in HIV treatment and thought to contribute to treatment-related lipodystrophy through alteration of SREBP-1, a transcriptional regulator expressed in liposarcoma, has been the subject of a clinical trial. Thus far, this class of agents has shown no proven benefit 56, 57 .…”

Section: Systemic Therapymentioning

confidence: 99%

Recent advances in the management of liposarcoma

Nassif

Tseng

Borges³

et al. 2016

F1000Res

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Liposarcoma is the most common soft tissue sarcoma. With its various subtypes, the natural history of this disease can vary significantly from a locally recurrent tumor to a highly malignant one carrying a poor prognosis. Progress in the understanding of the specific molecular abnormalities in liposarcoma provides greater opportunity for new treatment modalities. Although surgical resection and radiation therapy remain the keystones for the management of primary liposarcoma, the inclusion of novel agents that target known abnormalities in advanced liposarcoma enhances the potential for improved outcomes.

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Liposarcoma: molecular targets and therapeutic implications

Cited by 38 publications

References 67 publications

Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression

Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression

Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate‐grade or high‐grade liposarcoma

Recent advances in the management of liposarcoma

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