Please click on the links
For those who visit dsrct.com you will see a study that was started over 12 years for DSRCT —http://www.dsrct.com/Stehlin%20-%20Hope%20Newsletter%20(6-05).pdf
This study is now in clinical trial. Number is NCT02575638.
Note due to lack of funding there is no updated specific research for DSRCT.
See attached pdf1278268
Georgia Cancer Center researchers employing IBM’s Watson to rapidly assess genetic markers in …
The Augusta Chronicle
After setting up a few parameters – there isn’t even a category that covers the type of cancer he is sending, called desmoplastic small round cell tumor…
In this study, we assessed the response rate and progression free survival in nine cases of progressive DSRCT included in the OUTC’s registry and treated with antiangiogenics targeted agents (sunitinib, sorafenib and bevacizumab). OUTC’s, a French national registry, collects data about the use of off-label targeted therapy in sarcoma.
Generation of chromosomal translocations that lead to conditional fusion protein expression using CRISPR-Cas9 and homology-directed repair
EWSR1-WT1 translocation t(11;22)(p13;q12) found in DSRCT is modeled.
Aspirin may prevent cancer from spreading
New transcriptional-based insights into the pathogenesis of desmoplastic small round cell tumors (DSRCTs).
To gain new insights into desmoplastic small round cell tumors (DSRCTs) by means of gene expression profiling (GEP). Formalin-fixed, paraffin-embedded surgical specimens obtained from seven pretreated DSRCT patients were interrogated using GEP complemented by immunohistochemistry, a cancer stem cell array, and miRNA in situ hybridisation, including the combined chimera modules miRNA-200/ZEB1 and miRNA-34/SLUG. The chimera modules divided the cases into three classes that respectively recapitulated the traits of mesenchymal epithelial reverse transition (MErT), epithelial mesenchymal transition (EMT), and hybrid/partial EMT. This indicates a close correlation between the reprogramming governed by EMT regulators and DSRCT biology, which was further confirmed by miRNA-21 and is consistent with the broad morphological spectrum of DSRCTs. Starting from the miRNA-200/ZEB1 axis, we also found that DSRCTs carry a signature of immunological ignorance that is not responsive to PD–L1 blockade. Evidence that the up-regulation of miRNA-200 and E-cadherin, and quite a high level of miRNA-21 expression segregate with the MErT supports the idea that, in addition to the hybrid/partial state, MErT is also enriched in stemness: the androgen-positive cases, whose stemness traits were confirmed by stem cell arrays, all fell into these two classes. Our findings also confirmed that tumoral cell PDGFRA expression correlates with desmoplasia, and demonstrated the co-expression of PDGFRA and ISLR/Meflin, another marker of pluripotency. Despite the limited number of cases, these findings provide unexpectedly relevant information concerning the pathogenesis of DSRCTs, and prove the validity of miRNA-based chimera circuit modelling in the clinico-pathological setting.
We had our family member’s DSRCT sequenced at Dana Farber in Boston. If you or someone you care about has DSRCT please have their genome sequenced. The more copies of DSRCT will help research.
I also found this site. Looks interesting.
The CCC enables hospitals and research institutions to share patient genomic, imaging, and clinical data securely for potentially lifesaving discoveries.
Sarcoma is an aggressive form of cancer responsible for up to 20 percent of childhood cancers. Tumors often first appear in the extremities and the abdomen. Surgery is a primary treatment, but it often is combined with chemotherapy. Researchers now propose a scheme to target chemotherapy medications specifically to sarcomas, leading to greater efficacy and fewer side effects.
This is a case report of an EWS patient with metastatic disease recurrence <2 years following standard chemotherapy/radiation who achieved a durable and sustained complete response following two series of treatments with Vigil (GMCSF/bi-shRNA furin DNA autologous tumor immunotherapy) serially manufactured from first and second recurrences with ELISPOT assay correlation. Results support justification of further testing of Vigil with ELISPOT assay as a biomarker to assess level of immune response and correlation with disease control. You will need to create an account with smartpatients.com to access this http://goo.gl/EqcHzs
Mechanism of action of trabectedin in desmoplastic small round cell tumor cells
 enrolled 38 patients including 22 with Ewing’s Sarcoma and 16 with
desmoplastic small round cell tumor (DSRCT) into a Phase II study to test the
monoclonal antibody (MAb) IGF-1R inhibitor ganitumab (AMG479)
Several subtypes of difficult-to-treat sarcomas may respond to treatment with PD-1 pathway inhibiting immunotherapies, according to results presented at the 2017 European Cancer Congress of an immunohistochemistry (IHC) analysis of a large patient population. –
An immunohistochemistry (IHC) analysis of a large patient population demonstrated that several subtypes of difficult-to-treat sarcomas may respond to treatment with PD-1 pathway inhibiting immunotherapies, according to findings presented at the 2017 European Cancer Congress in Amsterdam1. – See more at: http://www.onclive.com/web-exclusives/pd1-blocakde-potential-comes-to-light-in-sarcoma-subtypes#sthash.AlolpvrV.dpuf
Abstract LB-238: Direct targeting of oncogenic transcription factors using next-generation oligonucleotides as a novel therapeutic strategy for translocation-positive sarcomas
….We have extensively characterized two new DSRCT cell lines harboring the characteristic oncogenic EWSR1-WT1 t(11;22)(p13;q12) fusion, and have used these tools to develop orthotopic xenograft models…
Morphoproteomic profiling of the mammalian target of rapamycin (mTOR) signaling pathway in desmoplastic small round cell tumor (EWS/WT1), Ewing’s sarcoma (EWS/FLI1) and Wilms’ tumor(WT1).
A 8-year survivor of unresectable intrapelvic desmoplastic small round cell tumor treated with concurrent chemoradiotherapy
BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models
The first large series of desmoplastic small round cell tumor was reported twenty-five years ago. This article reviews the original characterization of this neoplasm, and the eventual expansion of its clinical and pathological spectrum. Relevant data on its molecular features are summarized, in order to understand the search for therapeutic targets. The challenge ahead is to better know and cure this disease through the finding and validation of actionable therapeutic targets
DSRCT reviewed, discussing morphology and immunohistochemistry, molecular genetic findings, potential targeted treatments, and the differential diagnosis.
Novel secondary somatic mutations in Ewing’s sarcoma and desmoplastic small round cell tumors.
One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment.
These results suggested that rapamycin induces apoptosis by preventing the degradation of the Bax protein by the proteasome, and that this process is independent of mTOR inhibition. Furthermore, these results strongly support the introduction of the use of rapamycin as a cytotoxic agent for the treatment of DSRCT.
Abstract LB-238: Direct targeting of oncogenic transcription factors using next-generation oligonucleotides as a novel therapeutic strategy for translocation-positive sarcomas
Desmoplastic small round cell tumour successfully treated with caffeine-assisted chemotherapy: a case report and review of the literature.
From the article below
“Understanding the genomic aberrations and pathway abnormalities in DSRCT will be critical to the design of effective therapy. WT1 is a potential target for T-cell, natural killer cell or antibody-mediated immunotherapy. A number of downstream targets of the EWS-WT1 fusion protein such as insulin-like growth factor receptor  and platelet derived growth factor-A  are involved in growth factor signaling and could be inhibited with therapeutic benefit. Additionally, vascular endothelial growth factor- (VEGF-) A and VEGF receptor-2 are overexpressed in DSRCT  and the mTOR pathway is believed to be constitutively activated . To exploit the vascular nature of DSRCT and this differential overexpression of VEGF-A and VEGF receptor-2, bevacizumab is being added to conventional chemotherapy (irinotecan/temozolomide + P6 protocol) in a trial for the upfront treatment of these patients (NCT01189643). Other agents being evaluated for activity in DSRCT include antitype-1 insulin-like growth factor receptor antibodies  and multiple tyrosine kinase inhibitors [38–41]. MTOR-inhibitors were found to downregulate the expression of the EWS/WT1 transcript and increase the Bax/BcL-xL ratio resulting in increased tumor cell death [42, 43]. Another potentially targetable aberration that appears unique to DSRCT is the equilibrative nucleoside transporter 4 (ENT4). ENT4 is a pH-dependent adenosine transporter that is directly activated by EWS/WT1 and highly expressed in primary tumors and cell lines, making it an attractive therapeutic target. It remains to be seen whether targeting any of these pathways, alone or in combination , has the potential to make a significant impact on patient outcomes.”
Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor
A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease
A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease.
Not sure if I’m reading this right. It seems to be a study about environmental factors that may be associated with tumor initiation.
Molecular Changes Associated With Tumor Initiation and Progression of Soft Tissue Sarcomas: Targeting the Genome and Epigenome.
Curcumin is a naturally occurring polyphenolic compound found in the turmeric, which is used as food additive in Indian cooking and as a therapeutic agent in traditional Indian medicine. Curcumin is currently under investigation as a chemotherapeutic and chemopreventive agent in adult cancer models at both pre-clinical and clinical levels. In this preliminary study, we show that curcumin is effective in causing cell cycle arrest, inducing apoptosis, and suppressing colony formation in the Ewing sarcoma cell line SK-NEP-1. Curcumin causes upregulation of cleaved caspase 3 and downregulation of phospho-Akt, producing apoptosis in Ewing sarcoma cells at an inhibitory concentration 50% (IC50) of approximately 4 μM. Our findings indicate a need for further evaluation of curcumin in chemotherapy and chemoprevention of Ewing sarcoma
Cell cycle inhibition and apoptosis induced by Curcumin in Ewing sarcoma cell line SK-NEP-1.
From the American Institute for Cancer Research
Here’s a link that talks about COX-2 inhibitors. You have to scroll down to find in
From Miami hospital. Not specifically DSRCT, but rather sarcomas
In fact, researchers believe that, because some sarcomas are caused by something as simple as a translocation in a cell’s DNA, advances in sarcoma research might provide an opportunity for treatment developments in more genetically complex solid tumor cancers. Trent says he and his colleagues are using “smart bombs,” targeted therapy that focuses on a biological feature of the tumor to eradicate it.
Extracts From Reishi Mushroom And Green Tea Shows Synergistic Effect To Slow Sarcoma
Here’s a study
And this is from MSKCC
Cancer researchers have known for decades that tumours use a faster metabolism compared to normal cells in our body. One classic example of this is that cancer cells increase their consumption of glucose to fuel their rapid growth and strike against programmed cell death. This means that limiting glucose consumption in cancer cells is becoming an attractive tool for cancer treatments.
This is interesting. No study for DSRCT but still interesting.
ow, researchers have come up with an approach that tricks these spinoff tumors into swallowing poison.
Download pdf and do a search DSRCT to find relevant information
DSRCT has significant IHC expression of AR and c-Kit in heavily pre-treated patients. The presence of significant AR expression in 37% suggests that these patients could possibly respond to CAB. The significance of c-Kit expression in 35% of DSRCT patients is unknown and warrants further investigation.
On the old website dsrct.com there is mentioned of a study for DSRCT patients. Here’s the link.
We found Doug Coil and they are still developing this anti-cancer agent. To quote our last communication in 11/2015
We received some seed funding and are in the process of setting up a laboratory to continue making better derivatives of the extract. We feel we can tweak this molecule to significantly increase the effectiveness. If additional funds are secured, we have a new formulation (to overcome absorption issues) of a derivative already manufactured. If all goes well we will start treating patients Q1 of 2016.
Here are some links to the data
Thanks Doug and team for your continued hard work in developing this less toxic agent. Hope the trials go well.
We are familiar with one case, a 15-year survivor of DSRCT who has taken a COX-2 inhibitor since the completion of his treatment. Presently he is taking Celebrax, not sure of dosage. Is this really helping him? They don’t know for sure, but he has no plan to stop taking it.
Has any other DSRCT survivor taken a COX-2 inhibitor? Please let us know — click leave reply below.
The IRCI (International Rare Cancer Initiative) has an initiative to facilitate the development of international clinical trials for patients with rare cancers in order to boost the progress of new treatments for these patients. DSRCT is one they are studying!!
UPDATE: I spoke to one of the doctors involved. Their initiative has been stalled for a variety of reasons.
Founds some research on DSRCTP. Wonder if that is a variant of DSRCT? Curious what this chimeric protein is.
Desmoplastic small round cell tumor of the peritoneum (DSRCTP) is a rare tumor in the family of small round cell tumors that classically affects adolescent male. It is distinguished from other small round cell tumors by the balanced chromosomal translocation t(11;22)(p13;q12) involving the Ewing’s sarcoma/primitive neuroectodermal tumor gene (EWS) and Wilms’ tumor gene (WT1). This fusion product leads to production of a chimeric protein that can upregulate transcriptional activity.
Antiangiogenic agents that block vascular endothelial growth factor (VEGF) signaling are important components of current cancer treatment modalities but are limited by alternative ill-defined angiogenesis mechanisms that allow persistent tumor vascularization in the face of continued VEGF pathway blockade. We identified prostaglandin E2 (PGE2) as a soluble tumor-derived angiogenic factor associated with VEGF-independent angiogenesis. PGE2 production in preclinical breast and colon cancer models was tightly controlled by cyclooxygenase-2 (COX-2) expression, and COX-2 inhibition augmented VEGF pathway blockade to suppress angiogenesis and tumor growth, prevent metastasis, and increase overall survival. These results demonstrate the importance of the COX-2/PGE2 pathway in mediating resistance to VEGF pathway blockade and could aid in the rapid development of more efficacious anticancer therapies
In a recent study published in Nature Communications we showed that cancer cells stimulate the over-production of the protein known as PARP14, enabling them to use glucose to turbocharge their growth and override the natural check of cell death. Using a combination of genetic and molecular biology approaches, we have also demonstrated that inhibiting or reducing levels of PARP14 in cancer cells starves them to death.
There has been a great deal written about the use of selective cyclo-oxygenase-2 (COX-2) inhibitors in the adult population. Yet despite this there is still controversy over their place in treatment and in the interpretation of evidence from the major clinical trials.1 In the UK the National Institute for Clinical Excellence (NICE) recommended COX-2 inhibitors only be prescribed for osteoarthritis and rheumatoid arthritis patients at high risk of developing serious gastrointestinal adverse effects.2
Their role in children is even less well defined, with only a small number of published studies. Yet despite this lack of published evidence there is an undercurrent among paediatric practitioners to prescribe these agents. The aim of this review is to highlight the current published literature on the use of COX-2 inhibitors in children.
NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) is a clinical trial that analyzes patients’ tumors to determine whether they contain genetic abnormalities for which a targeted drug exists (that is, “actionable mutations”) and assigns treatment based on the abnormality. NCI-MATCH seeks to determine whether treating cancers according to their molecular abnormalities will show evidence of effectiveness.