bims-myxlip 2023-11-26 papers

Issue of 2023–11–26
three papers selected by
Laura Mannarino, Humanitas Research

Cancers (Basel). 2023 Nov 07. pii: 5308. [Epub ahead of print]15(22):

PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma.

Kirsi Toivanen, Sami Kilpinen, Kalle Ojala, Nanna Merikoski, Sami Salmikangas, Mika Sampo, Tom Böhling, Harri Sihto.

Liposarcomas (LPSs) are a heterogeneous group of malignancies that arise from adipose tissue. Although LPSs are among the most common soft-tissue sarcoma subtypes, precision medicine treatments are not currently available. To discover LPS-subtype-specific therapy targets, we investigated RNA sequenced transcriptomes of 131 clinical LPS tissue samples and compared the data with a transcriptome database that contained 20,218 samples from 95 healthy tissues and 106 cancerous tissue types. The identified genes were referred to the NCATS BioPlanet library with Enrichr to analyze upregulated signaling pathways. PDE3A protein expression was investigated with immunohistochemistry in 181 LPS samples, and PDE3A and SLFN12 mRNA expression with RT-qPCR were investigated in 63 LPS samples. Immunoblotting and cell viability assays were used to study LPS cell lines and their sensitivity to PDE3A modulators. We identified 97, 247, and 37 subtype-specific, highly expressed genes in dedifferentiated, myxoid, and pleomorphic LPS subtypes, respectively. Signaling pathway analysis revealed a highly activated hedgehog signaling pathway in dedifferentiated LPS, phospholipase c mediated cascade and insulin signaling in myxoid LPS, and pathways associated with cell proliferation in pleomorphic LPS. We discovered a strong association between high PDE3A expression and myxoid LPS, particularly in high-grade tumors. Moreover, myxoid LPS samples showed elevated expression levels of SLFN12 mRNA. In addition, PDE3A- and SLFN12-coexpressing LPS cell lines SA4 and GOT3 were sensitive to PDE3A modulators. Our results indicate that PDE3A modulators are promising drugs to treat myxoid LPS. Further studies are required to develop these drugs for clinical use.

Keywords: PDE3A; SLFN12; liposarcoma; myxoid

DOI: https://doi.org/10.3390/cancers15225308

Cells. 2023 Nov 15. pii: 2632. [Epub ahead of print]12(22):

Genomic Profiling and Clinical Outcomes of Targeted Therapies in Adult Patients with Soft Tissue Sarcomas.

Stefania Kokkali, Eleni Georgaki, Georgios Mandrakis, Claudia Valverde, Stamatios Theocharis.

Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still controversial in patients with sarcoma, given the low mutational burden and the lack of recurrent targetable alterations in most of the sarcoma histotypes. The clinical impact of genomic profiling in STS has not been investigated prospectively. A limited number of retrospective, mainly single-institution, studies have addressed this issue using various NGS technologies and platforms and a variety of criteria to define a genomic alteration as actionable. Despite the detailed reports on the different gene mutations, fusions, or amplifications that were detected, data on the use and efficacy of targeted treatment are very scarce at present. With the exception of gastrointestinal stromal tumors (GISTs), these targeted therapies are administered either through off-label prescription of an approved drug or enrollment in a matched clinical trial. Based mainly on anecdotal reports, the outcome of targeted therapies in the different STS histotypes is discussed. Prospective studies are warranted to assess whether genomic profiling improves the management of STS patients.

Keywords: DNA sequencing; RNA sequencing; actionable alterations; comprehensive genomic profiling; genetic aberration; next-generation sequencing; precision medicine; soft tissue sarcoma; targeted therapy

DOI: https://doi.org/10.3390/cells12222632

Med Sci (Basel). 2023 Nov 08. pii: 72. [Epub ahead of print]11(4):

Primary Orbital Myxoid Liposarcoma.

Miguel Armando Benavides-Huerto, Lourdes Páramo-Figueroa, Daniel Moreno-Páramo, Francisco Alejandro Lagunas-Rangel.

Although liposarcoma is the most prevalent soft tissue sarcoma in adults, head and neck liposarcomas are rare and account for less than 5% of all liposarcomas. The primary orbital location is even more exceptional, with fewer than 100 cases documented in the medical literature. Given the scarcity of cases of orbital liposarcoma and the limited familiarity of physicians and pathologists with this pathology, there is an increased risk of non-diagnosis or misdiagnosis, which may lead to inappropriate patient management. To address these challenges, we present a case of primary orbital myxoid liposarcoma and subsequently discuss the primary findings of this case based on the evidence documented in the medical literature. This comprehensive text is designed to serve as a valuable resource for healthcare professionals and pathologists, with the goal of promoting both clinical suspicion and accurate diagnosis and treatment of this rare condition in future cases.

Keywords: adipocyte; cancer; diagnosis; eye

DOI: https://doi.org/10.3390/medsci11040072