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EMBO Molecular Medicine Nov 2020Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the... (Review)
Review
Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.
Topics: Adolescent; Bone Neoplasms; Child; Humans; Molecular Medicine; Osteosarcoma; Sarcoma; Soft Tissue Neoplasms
PubMed: 33047515
DOI: 10.15252/emmm.201911131 -
Pathologica Apr 2021Mesenchymal tumours represent one of the most challenging field of diagnostic pathology and refinement of classification schemes plays a key role in improving the... (Review)
Review
Mesenchymal tumours represent one of the most challenging field of diagnostic pathology and refinement of classification schemes plays a key role in improving the quality of pathologic diagnosis and, as a consequence, of therapeutic options. The recent publication of the new WHO classification of Soft Tissue Tumours and Bone represents a major step toward improved standardization of diagnosis. Importantly, the 2020 WHO classification has been opened to expert clinicians that have further contributed to underline the key value of pathologic diagnosis as a rationale for proper treatment. Several relevant advances have been introduced. In the attempt to improve the prediction of clinical behaviour of solitary fibrous tumour, a risk assessment scheme has been implemented. NTRK-rearranged soft tissue tumours are now listed as an "emerging entity" also in consideration of the recent therapeutic developments in terms of NTRK inhibition. This decision has been source of a passionate debate regarding the definition of "tumour entity" as well as the consequences of a "pathology agnostic" approach to precision oncology. In consideration of their distinct clinicopathologic features, undifferentiated round cell sarcomas are now kept separate from Ewing sarcoma and subclassified, according to the underlying gene rearrangements, into three main subgroups (CIC, BCLR and not ETS fused sarcomas) Importantly, In order to avoid potential confusion, tumour entities such as gastrointestinal stroma tumours are addressed homogenously across the different WHO fascicles. Pathologic diagnosis represents the integration of morphologic, immunohistochemical and molecular characteristics and is a key element of clinical decision making. The WHO classification is as a key instrument to promote multidisciplinarity, stimulating pathologists, geneticists and clinicians to join efforts aimed to translate novel pathologic findings into more effective treatments.
Topics: Biomarkers, Tumor; Humans; Precision Medicine; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms; World Health Organization
PubMed: 33179614
DOI: 10.32074/1591-951X-213 -
Annals of Oncology : Official Journal... Nov 2021
Topics: Follow-Up Studies; Humans; Sarcoma; Soft Tissue Neoplasms
PubMed: 34303806
DOI: 10.1016/j.annonc.2021.07.006 -
Nature Communications Jun 2022There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive...
There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome this challenge by providing insight into sarcomas' molecular drivers. Through targeted panel sequencing of 7494 sarcomas representing 44 histologies, we identify highly recurrent and type-specific alterations that aid in diagnosis and treatment decisions. Sequencing could lead to refinement or reassignment of 10.5% of diagnoses. Nearly one-third of patients (31.7%) harbor potentially actionable alterations, including a significant proportion (2.6%) with kinase gene rearrangements; 3.9% have a tumor mutational burden ≥10 mut/Mb. We describe low frequencies of microsatellite instability (<0.3%) and a high degree of genome-wide loss of heterozygosity (15%) across sarcomas, which are not readily explained by homologous recombination deficiency (observed in 2.5% of cases). In a clinically annotated subset of 118 patients, we validate actionable genetic events as therapeutic targets. Collectively, our findings reveal the genetic landscape of human sarcomas, which may inform future development of therapeutics and improve clinical outcomes for patients with these rare cancers.
Topics: Biomarkers, Tumor; Bone Neoplasms; Genomics; Humans; Mutation; Osteosarcoma; Prospective Studies; Sarcoma
PubMed: 35705558
DOI: 10.1038/s41467-022-30496-0 -
International Journal of Molecular... Mar 2023Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological...
Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours [...].
Topics: Humans; Pathology, Molecular; Sarcoma; Incidence; Soft Tissue Neoplasms
PubMed: 36982907
DOI: 10.3390/ijms24065833 -
Journal of Hematology & Oncology Jul 2021Metabolic rewiring offers novel therapeutic opportunities in cancer. Until recently, there was scant information regarding soft tissue sarcomas, due to their... (Review)
Review
Metabolic rewiring offers novel therapeutic opportunities in cancer. Until recently, there was scant information regarding soft tissue sarcomas, due to their heterogeneous tissue origin, histological definition and underlying genetic history. Novel large-scale genomic and metabolomics approaches are now helping stratify their physiopathology. In this review, we show how various genetic alterations skew activation pathways and orient metabolic rewiring in sarcomas. We provide an update on the contribution of newly described mechanisms of metabolic regulation. We underscore mechanisms that are relevant to sarcomagenesis or shared with other cancers. We then discuss how diverse metabolic landscapes condition the tumor microenvironment, anti-sarcoma immune responses and prognosis. Finally, we review current attempts to control sarcoma growth using metabolite-targeting drugs.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Metabolic Networks and Pathways; Metabolome; Metabolomics; Sarcoma; Signal Transduction; Transcriptome; Tumor Microenvironment
PubMed: 34294128
DOI: 10.1186/s13045-021-01125-y -
International Journal of Molecular... Nov 2018Chromosomal translocations are observed in approximately 20% of soft tissue sarcomas (STS). With the advances in pathological examination technology, the identification... (Review)
Review
Chromosomal translocations are observed in approximately 20% of soft tissue sarcomas (STS). With the advances in pathological examination technology, the identification of translocations has enabled precise diagnoses and classifications of STS, and it has been suggested that the presence of and differences in translocations could be prognostic factors in some translocation-related sarcomas. Most of the translocations in STS were not regarded as targets of molecular therapies until recently. However, trabectedin, an alkylating agent, has shown clinical benefits against translocation-related sarcoma based on a modulation of the transcription of the tumor's oncogenic fusion proteins. Many molecular-targeted drugs that are specific to translocations (e.g., anaplastic lymphoma kinase and tropomyosin kinase related fusion proteins) have emerged. The progress in gene technologies has allowed researchers to identify and even induce new translocations and fusion proteins, which might become targets of molecular-targeted therapies. In this review, we discuss the clinical significance of translocation-related sarcomas, including their diagnoses and targeted therapies.
Topics: Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Forkhead Transcription Factors; Humans; Sarcoma
PubMed: 30487384
DOI: 10.3390/ijms19123784 -
International Journal of Molecular... Dec 2021Epigenetic changes influence various physiological and pathological conditions in the human body. Recent advances in epigenetic studies of the skin have led to an... (Review)
Review
Epigenetic changes influence various physiological and pathological conditions in the human body. Recent advances in epigenetic studies of the skin have led to an appreciation of the importance of epigenetic modifications in skin diseases. Cutaneous sarcomas are intractable skin cancers, and there are no curative therapeutic options for the advanced forms of cutaneous sarcomas. In this review, we discuss the detailed molecular effects of epigenetic modifications on skin sarcomas, such as dermatofibrosarcoma protuberans, angiosarcoma, Kaposi's sarcoma, leiomyosarcoma, and liposarcoma. We also discuss the application of epigenetic-targeted therapy for skin sarcomas.
Topics: Animals; Epigenesis, Genetic; Humans; Sarcoma; Skin Neoplasms; Treatment Outcome
PubMed: 35008848
DOI: 10.3390/ijms23010422 -
Cancer Metastasis Reviews Sep 2016Better diagnostic biomarkers and therapeutic options are still necessary for patients with sarcomas due to the current limitations of diagnosis and treatment. Exosomes... (Review)
Review
Better diagnostic biomarkers and therapeutic options are still necessary for patients with sarcomas due to the current limitations of diagnosis and treatment. Exosomes are small extracellular membrane vesicles that are released by various cells and are found in most body fluids. Tumor-derived exosomes have been proven to mediate tumorigenesis, intercellular communication, microenvironment modulation, and metastasis in different cancers, including in sarcomas. Recently, exosomes have been considered as potential biomarkers for sarcoma diagnosis and prognosis, and as possible targets for sarcoma therapy. Moreover, due to their specific cell tropism and bioavailability, exosomes can also be engineered as vehicles for drug delivery. In this review, we discuss recent advances in the roles of tumor-derived exosomes in sarcoma and their potential clinical applications.
Topics: Biological Transport; Biomarkers, Tumor; Cell Communication; Cell Fractionation; Cell Transformation, Neoplastic; Drug Delivery Systems; Exosomes; Humans; Immunotherapy; Neoplasm Metastasis; Prognosis; Sarcoma; Subcellular Fractions; Tumor Microenvironment
PubMed: 27342745
DOI: 10.1007/s10555-016-9630-4 -
Annals of Oncology : Official Journal... Dec 2021
Topics: Bone Neoplasms; Follow-Up Studies; Humans; Osteosarcoma; Sarcoma
PubMed: 34500044
DOI: 10.1016/j.annonc.2021.08.1995