Materiały źródłowe

• #1 Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7865637/

  Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. […] The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFR, VEGF and other proteins related to tumor and vascular cell proliferation. […] The up-regulation of PDGFR is a hallmark event in the development and DSRCT. […] The EWS-WT1 transcription factor translocation produces a chimeric protein that induces the expression of PDGFR that can explain the histological characteristics of DSRCT that is marked by profuse stromal proliferation and increased vascular density. […] Cytogenetic and molecular characterization of DSRCT identified a unique chromosomal rearrangement, t(11; 22)(p13; q12), associated with this tumor.

• #2 Primary desmoplastic small-round-cell tumor of the ovary | Journal of the Egyptian National Cancer Institute | Full Text

  https://jenci.springeropen.com/articles/10.1186/s43046-019-0001-4

  Desmoplastic small-round-cell tumor (DSRCT) is an extremely rare and highly aggressive malignancy. It is of yet unclear origin, but it is assumed to be of a mesothelial origin based on its tendency for widespread metastasis in serosal linings. […] This malignant entity with its atypical clinical, pathological, radiological features, aggressive course, and extensive intra-abdominal dissemination may confer a diagnostic dilemma when it is first encountered. […] Desmoplastic small-round-cell tumor arises from mesenchymal cells of the abdominopelvic peritoneum. The gene fusion between Ewing sarcoma (EWS) and WT1 genes resulting in the characteristic translocation t(11;22)(p13;q12), is the unique molecular hallmark and no other genetic factor has been linked to this aggressive tumor. […] Despite relapse which was reported in most of the patients during long-term follow-up, prolonged progression-free survival was best reported after multimodality treatment.

• #3 Desmoplastic small round cell tumors – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/dsrct/symptoms-causes/syc-20355405

  Desmoplastic small round cell tumors (DSRCT) are a type of cancer that often begins in the abdomen. […] Desmoplastic small round cell tumors are rare cancers that begin as a growth of cells. The growths often form on the tissue that lines the inside of the abdomen and pelvis. […] It’s not clear what causes desmoplastic small round cell tumors. […] Cancer begins when a cell develops changes in its DNA. A cell’s DNA contains the instructions that tell a cell what to do. The changes tell the cell to multiply quickly. This creates a clump of cancer cells called a tumor. The cancer cells can invade and destroy healthy body tissue. In time, the cancer cells can break away and spread to other parts of the body. […] Healthcare professionals haven’t found many risk factors for desmoplastic small round cell tumors. This cancer can happen to anyone, but it’s more common in young men and boys.

• #4 Transcriptome analysis of desmoplastic small round cell tumors identifies actionable therapeutic targets: a report from the Children’s Oncology Group | Scientific Reports

  https://www.nature.com/articles/s41598-020-69015-w

  To further understand the molecular pathogenesis of desmoplastic small round cell tumor (DSRCT), a fatal malignancy occurring primarily in adolescent/young adult males, we used next-generation RNA sequencing to investigate the gene expression profiles intrinsic to this disease. […] The hallmark molecular characteristic of DSRCT is a reciprocal t(11;22)(p13;q12) translocation involving the EWSR1 and the WT1 genes, identified in 1994. […] Although, these studies provide certain insights into the potential oncogenic pathways involved in DSRCT, gaps in our understanding of DSRCT biology hampers our ability to identify and prioritize possible therapeutic targets. […] Our study highlights the importance of defining DSRCTs by its hallmark translocation as the two tumor samples in our cohort that were negative for the EWS-WT1 fusion but were diagnosed as DSRCT histologically, had clearly distinct gene expression profiles as compared to the fusion positive tumors.

• #5 Mechanism of action of trabectedin in desmoplastic small round cell tumor cells | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3091-1

  Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive disease, that can be described as a member of the family of small round blue cell tumors. The molecular diagnostic marker is the t(11;22)(p13;q12) translocation, which creates an aberrant transcription factor, EWS-WT1, that underlies the oncogenesis of DSRCT. […] This unique chromosomal translocation provides the definitive molecular diagnostic marker of DSRCT and creates an aberrant transcription factor, EWS-WT1, which underlies the oncogenesis. […] The EWS-WT1 is considered the pathogenic lesion of DSRCT. It is composed of the N-terminal domain of the EWS gene and of the C-terminal DNA binding domain of the WT1 tumor suppressor gene. […] Since the EWS-WT1 chimera does not contain the first of the four zinc fingers of WT1, it has been reported that an altered DNA binding domain may be essential for cellular transformation in DSRCT.

• #6 Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11319132/

  Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive pediatric cancer caused by a reciprocal translocation between chromosomes 11 and 22, leading to the formation of the EWSR1::WT1 oncoprotein. […] The EWSR1::WT1 oncogene is a transcription factor formed by the fusion of the N-terminal activating domain of EWSR1 with the final three zinc fingers at the C-terminus of WT1. […] The essentiality of EWSR1::WT1 has been established with shRNA knockdown in vitro in five independent studies across five DSRCT cell lines and more recently in vivo using doxycycline-inducible shRNA depletion of EWSR1::WT1 in 3 cell line-derived xenografts. […] Recent studies have established sets of genes commonly regulated by EWSR1::WT1 across cell lines including a set of 68 upregulated and 223 downregulated genes identified across 2 cell lines by Gedminas et al., 2020 and a set of 175 upregulated and 166 downregulated genes identified across 4 cell lines in our lab.

• #7 Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

  https://www.mdpi.com/2072-6694/13/3/498

  Cytogenetic and molecular characterization of DSRCT identified a unique chromosomal rearrangement, t(11; 22)(p13; q12), associated with this tumor. The EWS-WT1 is the driver to tumorigenesis of DSRCT and it acts by up-regulating the expression of several genes. The chimeric product of the EWS-WT1 fusion protein acts as a dominant transcriptional activator factor that regulates the expression of several growth factor genes, including PDGFRA, IGF1R, EGFR, IL2, IL15 and also transcriptional factors such as MYC, PAX2 and WT1. The up-regulation of PDGFRα is a hallmark event in the development and DSRCT. The role of PDGFRα in the physiologic healing process is well described and is responsible for collagenous stromal production, inflammatory cell infiltration, especially macrophage chemotaxis and neo-angiogenesis, induces proliferation and is a chemo-attractant to fibroblasts and endothelial cells. The development and growth of DSRCT is primarily dependent on this translocation product. The EWS-WT1 transcription factor translocation produces a chimeric protein that induces the expression of PDGFRα that can explain the histological characteristics of DSRCT that is marked by profuse stromal proliferation and increased vascular density.

• #8 Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11319132/

  Integrating this gene expression data and WT1-directed ChIP-seq, we found that EWSR1::WT1 binding predominantly leads to upregulation or stable gene expression, with only 10% of EWSR1::WT1 bound genes negatively regulated by the fusion protein. […] A unique aspect of EWSR1::WT1 is its existence in two isoforms (E + KTS and E-KTS) which vary based on the inclusion or exclusion of three amino acids between zinc fingers 3 and 4 of the WT1 DNA binding domain. […] Given the differences in isoform transcriptional activity, an important question in DSRCT biology is whether one, the other, or both isoforms are necessary to induce oncogenesis. […] These data strongly suggest additional alterations or epigenetic states are necessary for EWSR1::WT1 induced oncogenesis. […] Other mechanistic questions that require further investigation include the role of EWSR1::WT1 in altering the chromatin landscape and whether it has oncogenic functions independent of its role as a transcription factor.

• #9 Multi-site desmoplastic small round cell tumors are genetically related and immune-cold | npj Precision Oncology

  https://www.nature.com/articles/s41698-022-00257-9

  Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue sarcoma that is characterized by the EWSR1-WT1 fusion protein. […] DSRCT is characterized by the translocation, t(11;22)(p13;q12) which results in the EWSR1-WT1 gene fusion. […] The loss of the proximal zinc fingers of WT1 in the chimeric fusion protein converts WT1 from a transcriptional repressor to an activator and presumably initiates the oncogenic process in DSRCT. […] Recent studies using cell and mouse models have demonstrated that the EWSR1-WT1 fusion can transform mouse embryonic fibroblasts and has pronounced effects on the proliferation, viability, and growth of DSRCT cells. […] This transformation may be directed by several downstream targets of the EWSR1-WT1 fusion including growth factor/receptor genes (e.g. IGF2, IGF1R, EGFR, FGFR4, PDGFA, VEGFR), transcriptional regulators (e.g., MYC, PAX2), matrix cellular genes (e.g., CDH1, CTGF), and others (e.g., AR, PARP).

• #10 Desmoplastic small round cell tumour: characteristics and prognostic factors of 41 patients and review of the literature | Clinical Sarcoma Research | Full Text

  https://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/2045-3329-3-14

  Desmoplastic small round cell tumour (DSRCT) is a rare but highly aggressive neoplasm that typically occurs in adolescent and young males. […] These cells co-express epithelial, mesenchymal, myogenic and neural markers, but are distinguished by the chromosomal translocation t(11;22)(p13;q12) resulting in the fusion of the Ewings sarcoma (EWSR1) and the Wilms tumour (WT1) genes. […] The understanding of this mechanism has provided a novel target for the treatment of this disease. […] Chromosomal translocation resulting in the fusion of the EWSR1 and WT1 genes is the molecular characteristic of DSRCT. […] The resulting fusion protein has been found to activate the IGF-1R gene promoter, causing the expression of this anti-apoptotic receptor tyrosine kinase.

• #11 Transcriptome analysis of desmoplastic small round cell tumors identifies actionable therapeutic targets: a report from the Children’s Oncology Group | Scientific Reports

  https://www.nature.com/articles/s41598-020-69015-w

  Our data goes on to show that DSRCT cluster independently of other fusion positive sarcomas that arise in patients within the same age range. […] Our study also shows that IGF2 is among the most highly expressed genes in both molecularly confirmed DSRCT tissues as well as an established DSRCT cell line. […] Our data further confirms FGFR4 to be a downstream target of EWS-WT1. […] Our finding of increased expression of CD200 in DSRCT tumors warrants further detailed investigation of this pathway as a potential therapeutic strategy in this disease and will be the focus of future studies.

• #12 Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7865637/

  The EWS-WT1 is the driver to tumorigenesis of DSRCT and it acts by up-regulating the expression of several genes. […] Our group published a study with comprehensive molecular profiling of a patient with the diagnosis of DSRCT. […] More recently, the molecular analysis of 6 patients with DSRCT revealed a total of 137 somatic mutations which were related to specific biological processes: DNA damage-response (DDR) network and mesenchymal-epithelial reverse transition/epithelial-mesenchymal transition (MErT/EMT), reinforcing the relevance of these processes in tumor heterogeneity, aggressiveness and drug resistance. […] There are many similarities between DSRCT and Ewing Sarcoma (ES) family tumors. Most of these tumors carry the EWS translocation. However, one important molecular aberration that distinguishes DSRCT from ES is the increased Androgen Receptor (AR) expression.

• #13 Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

  https://www.mdpi.com/2072-6694/13/3/498

  More recently, the molecular analysis of 6 patients with DSRCT revealed a total of 137 somatic mutations which were related to specific biological processes: DNA damage-response (DDR) network and mesenchymal–epithelial reverse transition/epithelial–mesenchymal transition (MErT/EMT), reinforcing the relevance of these processes in tumor heterogeneity, aggressiveness and drug resistance. There are many similarities between DSRCT and Ewing Sarcoma (ES) family tumors. Most of these tumors carry the EWS translocation. However, one important molecular aberration that distinguishes DSRCT from ES is the increased Androgen Receptor (AR) expression.

• #14 Multi-site desmoplastic small round cell tumors are genetically related and immune-cold | npj Precision Oncology

  https://www.nature.com/articles/s41698-022-00257-9

  Although patients all harbor the EWSR1-WT1 driver mutation, there is substantial heterogeneity in treatment response and survival outcomes among DSRCT patients. […] Our DSRCT samples had a low mutation rate (median of 0.72 mutations per Mb), with a median of 23 non-silent mutations per tumor, which is similar to other fusion-driven sarcomas such as Ewing sarcoma, synovial sarcoma, and rhabdomyosarcoma. […] Given the low prevalence of gene-level mutations, we interrogated whether pathways were recurrently altered by mapping all the mutated genes to pathways. […] The majority of these SCNAs involved entire chromosome arms or whole chromosomes, with very few significant focal events. […] Our phylogenetic tree analyses using both point mutation and SCNA data suggest that different tumors from the same DSRCT patients have a shared origin and are closely related.

• #15

  https://juniperpublishers.com/ijcsmb/IJCSMB.MS.ID.555618.php

  Recent advances in the understanding of the molecular pathophysiology of DSRCT should lead to the development of effective molecularly targeted therapies with fewer side effects. […] The development of molecularly targeted agents, likely in combination with conventional approaches, could potentially have significant impact on the treatment of this disease.

• #16 Multi-site desmoplastic small round cell tumors are genetically related and immune-cold | npj Precision Oncology

  https://www.nature.com/articles/s41698-022-00257-9

  The EWSR1-WT1 fusion is almost certainly a major driver in the early development and dispersion of DSRCT tumors. […] Therefore, until compounds that directly inhibit the EWSR1-WT1 fusion are developed, the best short-term strategy to eradicating this aggressive pediatric sarcoma is indirect targeting of pathways that the EWSR1-WT1 fusion relies on to mediate tumor growth and survival. […] Similar to other types of fusion-driven sarcomas such as synovial sarcoma, our DSRCT samples had lower overall immune infiltrate than other tumors types, especially those against which ICI are effective. […] This low level of immune infiltrate may be associated primarily with the low mutation burden in DSRCT.

• #17 Desmoplastic Small Round-cell Tumor: Retrospective Review of Institutional Data and Literature Review | Anticancer Research

  https://ar.iiarjournals.org/content/41/8/3859

  Due to the morphological overlap of DSCRT with other types of neoplasm, definitive diagnosis is dependent on molecular analysis by cytogenetics and in situ hybridization or reverse transcriptase polymerase chain reaction studies. […] DSCRT is characterized by the specific t(11;22)(p13;q12) translocation, with EWSR1WT1 gene fusion in the majority of cases. […] Identifying other genes that may assist with risk assessment of this rare disease is important. […] In the present study, we have described our experience with novel agents involving anti-vascular endothelial growth factor, multi-kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors. […] A substantial number of DSRCTs overexpress vascular endothelial growth factor receptor-2, and a handful of patients have had clinical responses to sunitinib, sorafenib, or pazopanib.

• #18

  http://waocp.com/journal/index.php/apjcc/article/view/1022

  DSRCT is known to be at least somewhat chemosensitive and radiosensitive. […] Novel treatment methods using precision oncology are essential in managing this disease. There is emerging data indicating the possible involvement of the mTOR pathway in DSRCT. […] In conclusion, DSRCT is a rare and aggressive disease and fatal for the majority of patients at this point in time. A definite treatment protocol has not been devised owing to the uncommonness of the disease.

• #19 CXCR4-Directed Imaging and Endoradiotherapy in Desmoplastic Small Round Cell Tumors | Journal of Nuclear Medicine

  https://jnm.snmjournals.org/content/64/9/1424

  Desmoplastic small round cell tumor (DSRCT) is a rare, radiosensitive, yet difficult-to-treat sarcoma subtype affecting predominantly male adolescents. […] The recurrent balanced chromosomal translocation t(11:32)(p13;q12) is a pathognomonic hallmark and a driver of the disease. […] DSRCT is characterized by immunologic ignorance. […] Because of the lack of clinical trials in this orphan disease, with approximately 1,000 patients reported to date, no standard therapy has been established. […] CXCR4 was first identified as a coreceptor for HIV (X4-tropic isolates) entry into cells. Beyond its role in various physiologic processes, including embryogenesis, angiogenesis, and modulation of hematopoietic stem cells, CXCR4 has gained attention because it is overexpressed in more than 20 different tumor entities, including sarcoma, with higher receptor expression denoting poor prognosis.

• #20 CXCR4-Directed Imaging and Endoradiotherapy in Desmoplastic Small Round Cell Tumors | Journal of Nuclear Medicine

  https://jnm.snmjournals.org/content/64/9/1424

  In particular, among sarcomas, CXCR4 overexpression has been previously described in Ewing sarcoma, which shares many biologic features with DSRCT, providing a rationale for exploring and targeting CXCR4 in DSRCT. […] We validated CXCR4 as a diagnostic biomarker and a promising target for endoradiotherapy in DSRCT, demonstrated its feasibility, and provided the first evidence of its clinical efficacy.

• #21 Primary desmoplastic small round cell tumour of the prostate | Journal of Clinical Pathology

  https://jcp.bmj.com/content/78/1/64

  DSRCT poses several challenges in differential diagnosis due to its resemblance to various malignancies with small round cell morphology, notably Ewings sarcoma (EWS), alveolar rhabdomyosarcoma (ARMS) and synovial sarcoma. […] The treatment of DSRCT remains challenging. The conventional treatment for DSRCT includes surgical resection, chemotherapy and radiation therapy. Other treatment methods such as high-dose alkylating agent chemotherapy and trial complete cytoreductive surgery have been used. Recent research indicated that CDK4/6 inhibitors may serve for targeted therapy of DSRCT.

• #22 Novel Secondary Somatic Mutations in Ewing’s Sarcoma and Desmoplastic Small Round Cell Tumors | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093676

  Ewing’s sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. […] Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%)); KRAS (n=1), PTPRD (n=1), GRB10 (n=2), MET (n=2) and PIK3CA (n=1). […] We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy.

• #23 Novel Secondary Somatic Mutations in Ewing’s Sarcoma and Desmoplastic Small Round Cell Tumors | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093676

  Here we report potential actionable mutations identified in four patients with advanced ES and in two patients with advanced DSRCT. The mutations include KRAS (G13N), PTPRD (W775D), GRB10 (Q107stop and V109A), MET (T1010I and N375S) and PIK3CA (M1040I and G1049S). Correlations with response and resistance to IGF1R inhibitor based regimen in these patients are discussed. […] Our study shows that 21.4% of patients (6 of 28) with advanced, heavily pretreated Ewing’s sarcoma family of tumors (ES, n=18; DSRCT, n=10) had secondary somatic molecular aberrations, including mutations in KRAS, PTPRD, GRB10, MET and PIK3CA. […] The specific genetic aberrations and their correlation with response and resistance may be also illuminating. […] In addition to the mutations in GRB10 and PTPRD that can directly affect IGF-1R signaling, an unexpected mutation in MET was identified in patients with ES and DSRCT.

• #24 Desmoplastic small-round-cell tumor – Wikipedia

  https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor

  This translocation is seen in virtually all cases of DSRCT. […] On immunohistochemistry, these cells have trilinear coexpression including the epithelial marker cytokeratin, the mesenchymal markers desmin and vimentin, and the neuronal marker neuron-specific enolase. Thus, although initially thought to be of mesothelial origin due to sites of presentation, it is now hypothesized to arise from a progenitor cell with multiphenotypic differentiation. […] The entity was first described by pathologists William L. Gerald and Juan Rosai in 1989.

• #25 Desmoplastic small round cell tumor: the report of two cases and literature analysis review of the radiological findings – Chen – Quantitative Imaging in Medicine and Surgery

  https://qims.amegroups.org/article/view/114164/html

  Desmoplastic small round cell tumor (DSRCT) is a rare, unique, and highly malignant tumor that tends to occur in children and adolescents. DSRCT has an occult onset and rapid disease progression and is susceptible to implantable spread and blood and lymphatic metastasis, which most often occurs in the liver, followed by the lungs, lymph nodes, and bones. […] DSRCT is characterized by chromosomal translocations that result in gene fusion involving EWSR1 and Wilms tumor 1 (WT1). Therefore, the EWS-WT1 fusion gene has high sensitivity and specificity for the diagnosis of DSRCT. […] The diagnosis of DSRCT relies on pathology and immunohistochemistry. Histopathological examination demonstrates nests, cords, and sheets of small round cells embedded in the desmoplastic stroma. Immunological phenotyping shows the multidirectional differentiation of tumor cells, which can express a variety of immunophenotypes including epithelial (EMA and keratin), neural (NSE), and mesenchymal (vimentin and desmin) markers.

• #26 ThinPrep Cytological Findings of Desmoplastic Small Round Cell Tumor with Extensive Glandular Differentiation: A Case Study

  https://www.jpatholtm.org/journal/view.php?doi=10.4132/KoreanJPathol.2013.47.2.182

  Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive neoplasm. The cytological diagnosis of this tumor has only occurred in a few cases, and most of these cases were based on fine-needle aspiration cytology. […] The most distinct cytological feature of DSRCT compared to the other small round cell tumors, is its stromal fibrillary fragment, which is not a commonly found in body fluid, and can only be found using fine-needle aspiration cytology. […] Immunohistochemically, DSRCT may show a various differentiation, which is a striking feature of the tumor. Typically, tumor cells are immunoreactive for epithelial (keratin and epithelial-membrane antigen), mesenchymal (vimentin), myogenic (desmin), and neural (neuron-specific enolase and CD56) markers. […] The most well known molecular event was a specific reciprocal translocation t(11; 22)(p13; 12).

• #27 A Case of Desmoplastic Small Round Cell Tumor Diagnosed in a Young Female Patient

  https://www.e-crt.org/journal/view.php?number=187

  Desmoplastic small round cell tumor (DSRCT) is a very rare malignancy, which was 1st described by Gerald and Rosai in 1989. […] Although its origin has not been identified, DSRCT is believed to arise from the mesothelium, because it is frequently found in the mesothelial-lined surface. Typical pathologic findings include abundant desmoplastic stroma and poorly differentiated small cells, which have various differentiations such as epithelial, mesenchymal, or neuronal differentiation. […] DSRCT and Ewing sarcoma/PNET (primitive neuroectodermal tumor) have EWS gene translocations. […] The tumor expressed CD99, which is highly sensitive to Ewing sarcoma/PNET. However, many other small round cell tumors including DSRCT can express CD99 on their surfaces. […] DSRCT and Ewing sarcoma/PNET have EWS gene translocations, which enable discrimination of these tumors from the other tumors. […] The differential diagnosis of these diseases can be made using RT-PCR. […] Molecular genetic methods such as FISH or RT-PCR could be helpful in diagnosis of DSRCT.

• #28 Desmoplastic Small Round-cell Tumor: Retrospective Review of Institutional Data and Literature Review | Anticancer Research

  https://ar.iiarjournals.org/content/41/8/3859

  Some have implicated a stem cell hypothesis in DSRCT based on the relative insensitivity of the tumor to high-dose chemotherapy. […] Unlike Ewing sarcoma, CD133+ stem cells have not yet been identified in DSCRT. […] Aggressive chemotherapy followed by stem cell therapy has been proposed but is not supported by evidence to date. […] Overall median survival was 17.8 (range=11.2-30.6) months. […] Despite aggressive therapy, outcomes continue to be poor and patient preferences on quality of life should be an important consideration in the decision-making process.

• #29

  https://juniperpublishers.com/ijcsmb/IJCSMB.MS.ID.555618.php

  Desmoplastic small round cell tumor (DSRCT) is an aggressive malignant neoplasm of young male adults and distant metastases occurs at the time of diagnosis. […] EWS-WT1 fusion protein and (11;22) (p13;q12) translocation, the N-terminal domain of EWS to the C-terminal DNA-binding domain of WT1 is the pathogenesis resulting in an aberrant transcription factor. […] DSRCT presents as an aggressive tumor with abdominal mass. […] More than 40% of patients have distant metastases at the time of diagnosis, mostly located in the liver, lungs, and lymph nodes. […] Although DSRCTs are generally sensitive to chemotherapy, the response is not enough to achieve cure since patients almost invariably relapse. […] This could potentially be a reflection of the heterogeneity of the cells within the tumor, where a distinct population of cells (cancer stem cells) that are less sensitive to chemotherapy and radiotherapy possess the ability to self-renew and retain the capacity to regenerate the tumor bulk after it has been eradicated.

• #30 Mechanism of action of trabectedin in desmoplastic small round cell tumor cells | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3091-1

  We found that EWS-WT1 transcript levels are affected by trabectedin treatment, to a slight but significative degree, and that the drug causes a quantitative decrease in the binding of the aberrant transcription factor to its target promoters. Therefore the decrease of chimera binding might be due at least in part to the decrease in EWS-WT1 transcripts produced in the cell after drug treatment, not only to a direct effect of trabectedin on the binding. […] However, expression profiling results suggested that trabectedin has significant effects on the transcriptional programs of JN-DSRCT-1 cells: in particular genes involved in apoptosis are induced and genes involved in proliferation are inhibited at early time points after drug treatment. […] The heterogeneity of EWS-WT1 transcripts represents an obstacle to the precise definition of the mode of action of trabectedin or other potential drugs, indicating the need of other cellular models for this disease.

• #31 SciELO Brazil – Desmoplastic Small Round Cell Tumor of the Ovary: A Case Report with a New Modality of Treatment and Review of the Literature Desmoplastic Small Round Cell Tumor of the Ovary: A Case Report with a New Modality of Treatment and Review of t

  https://www.scielo.br/j/rbgo/a/3Xxpmvtt8Pdt9x46cybVkwB/?lang=en

  We demonstrated the efficiency of the treatment modality chosen in this case, which combined primary and secondary surgical debulking, CWS chemotherapy protocol, and boost radiotherapy joined with high-dose chemotherapy followed by autologous stem cell support. […] An increasing number of patients has been diagnosed with DSRCT over past decade, and, with improvement of our overall knowledge, especially about the molecular mechanisms and signal pathways involved in the tumor pathogenesis, we can expect further advances in treatment.

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