Desmoplastic small round blue cell tumors (DSRCTs) originate from a cell with multilineage potential. A molecular hallmark of DSRCT is the EWS-WT1 reciprocal translocation. Ewing sarcoma and DSRCT are treated similarly due to similar oncogene activation pathways, and DSRCT has been represented in very limited numbers in sarcoma studies. Despite aggressive therapy, median survival ranges from 17 to 25 months, and 5-year survival rates remain around 15%, with higher survival reported among those undergoing removal of at least 90% of tumor in the absence of extraperitoneal metastasis. Almost 100% of these tumors contain t(11;22) (p13;q12) translocation, and it is likely that EWS-WT1 functions as a transcription factor possibly through WT1 targets. While there is no standard protocol for this aggressive disease, treatment usually includes the neoadjuvant HD P6 regimen (high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV) alternating with ifosfamide and etoposide (IE) chemotherapy combined with aggressively attempted R0 resection). We aimed to review the molecular characteristics of DSRCTs to explore therapeutic opportunities for this extremely rare and aggressive cancer type.

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dissemination and therapy resistance in PADC via activation of down-stream pathways such as PI3K/AKT and Ras/Raf/MAPK. This family is overexpressed in 42-90% of PDAC, which associates with disease progression and poor overall survival. Despite the key roles of the ErbB family in initiation and malignant progression of PDAC, clinical trials with ErbB-targeting agents such as erlotinib, gefitinib, cetuximab, trastuzumab and lapatinib have been disappointing. In this preclinical study, we investigated the anti-tumor activities of dacomitinib, a pan-inhibitor of the ErbB receptors, in PDAC cell lines. Methods: MTT assay was performed to evaluate cell viability. qRT-PCR was conducted to measure the expression levels of FOXM1, c-Myc, AURKB, N-cadherin and TWIST1. Propium iodide staining was performed to analyze cell cycle distribution and Annexin/ PI assay was carried out to evaluate induction of apoptosis. We performed Western blot analysis to measure the expression levels of survivin, Bcl-2, p21, XIAP, Mcl1, cIAP1, cIAP2, FOXM1, cyclin B1, CDC25C, AURKB, CDK1, and EMT markers N-cadherin, Snail, ZEB1 and Twist1. Results: This report showed the advantage of pan-inhibition of the ErbB receptors by dacomitinib, as compared to the single targeted therapy agents including cetuximab, gefitinib, trastuzumab, H3.105.5 (anti-HER3 mAb) and lapatinib. Dacomitinib, but not the other agents, inhibited cell growth and induced apoptosis via reduction of the protein levels of survivin, Bcl-2, XIAP, Mcl1, cIAP1, cIAP2, FOXM1, cyclin B1, CDC25C, AURKB and CDK1. Moreover, dacomitinib decreased the expression of the EMT markers. Conclusions: These finding suggest that blockade of the ErbB receptors has more antitumor efficacy compared to single or dual blocking in this family. Moreover, our results provide a rationale for further investigation on the therapeutic potential of dacomitinib in treatment of the PADC.

Background: Urachal carcinoma is a rare entity that represents a small fraction (less than 0.5%) of primary bladder cancer. Although standard therapy for urachal carcinoma is not established, platinum-based chemotherapy is commonly used in clinical practice. We aimed to evaluate feasibility of S-1 plus cisplatin combination chemotherapy (SP) in patients with urachal carcinoma. Methods: A retrospective analysis of consecutive patients with urachal carcinoma who received SP (S-1 40-60 mg twice daily for 21 days plus cisplatin 60 mg/m2 on day 8, every 5 weeks) at our institution from April 2008 to March 2017 was performed. Combination therapy was continued up to 8 cycles. Following S-1 monotherapy was applied to some cases. Results: Seven of 12 patients with urachal carcinoma received SP chemotherapy. Six males and one female, and the median age was 54 (range: 49-68). Symptoms at initially diagnosed were as follows; macroscopic hematuria (n ¼ 4), stomach bloating (n ¼ 1), back pain (n ¼ 1) and no symptom (n ¼ 1; pulmonary metastases were detected on health checkup). SP was performed as adjuvant chemotherapy in 3 cases and as treatment for metastatic disease in 4 cases. Locations of metastatic organ were as follows; lung (3 cases), bone (3 cases), peritoneum (3 cases) and pleura (1 case; overlapping data). Median follow-up was 147 days (range: 10-1197) and median number of course was 4 (range: 1-8). Median duration of treatment was 147 days (range: 12-361). Reasons for discontinuation of treatment were as follows; progressive disease (n ¼ 2), adverse events (n ¼ 2), and treatment complete (n ¼ 1). Two patients are under treatment. Most common adverse events were neutropenia (Grade 2/1: 1/1 cases), anemia (Grade 3/2/1: 1/1/1 cases), appetite loss (Grade 3/2/1: 1/1/1 cases), general malaise (Grade 2/1: 1/1 cases), diarrhea (Grade 3: 2 cases) and pigmentation (Grade 1: 2 cases). One death from acute coronary syndrome occurred and was suspected to be treatmentrelated. Short-term efficacy evaluation of 4 metastatic patients were stable disease for 3 patients and progressive disease for 1 patient. Conclusions: Adverse events of SP were similar to those reported previously. The evaluation for long-term efficacy of SP for patients with urachal carcinoma was warranted.