Androgen and c-Kit receptors in desmoplastic small round cell tumors resistant to chemotherapy: novel targets for therapy

Fine, Robert L.; Shah, Samir S.; Moulton, Thomas; Yu, Ing Ru; Fogelman, David R.; Richardson, Michael; Burris, Howard A.; Samuels, Brian L.; Assanasen, Chatchawin; Gorroochurn, Prakash; Hibshoosh, Hanina; Orjuela, Manuela; Garvin, James H.; Goldman, Frederick D.; Dubovsky, D; Walterhouse, David; Halligan, Gregory E.

doi:10.1007/s00280-006-0280-z

Cited by 43 publications

(42 citation statements)

References 33 publications

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“…Some of these tumors express androgen receptors and produce CA-125 [181,182]. Approximately a third of DSRCTs express c-Kit [181]. According to a recent Mayo Clinic review, this disease is uniformly fatal [183].…”

Section: Molecular Pathology and Geneticsmentioning

confidence: 97%

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Adult human sarcomas. I. Basic science

Sinkovics¹

2007

Expert Review of Anticancer Therapy

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When connective tissue undergoes malignant transformation, glioblastomas and sarcomas arise. However, the ancient biochemical mechanisms, which are now operational in sarcomas distorted by mutations and gene fusions in misaligned chromosomes, were originally acquired by those cells that emerged during the Cambrian explosion. Preserved throughout evolution up to the genus Homo, these mechanisms dictate the apoptosis- and senescence-resistant immortality of malignant cells. A 'retroviral paradox' distinguishes human sarcomas from those of the animal world. In contrast to the retrovirally induced sarcomatous transformation of animal (avian, murine, feline and simian) cells, human sarcomas have so far failed to yield a causative retroviral isolate. However, the proto-oncogenes/oncogenes transduced from their host cells by retroviruses of animals are the same that are active in human sarcomas. Since the encoded oncoproteins arise after birth, they are recognized frequently by the immune system of the host. Immune lymphocytes that kill autologous sarcoma cells in vitro commonly fail to do so in vivo. Sarcoma vaccines generate immune T- and natural killer cell reactions; even when vaccinated patients do not show a clinical response, their tumors become more sensitive to chemotherapy. The aim of this review is to lay a solid molecular biological foundation for the conclusion that targeting the sarcoma oncogenes will result in regression of the disease.

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Section: Molecular Pathology and Geneticsmentioning

confidence: 97%

“…The desmoplastic appearance of these tumors is consequential to the constitutive activation of platelet-derived growth factor (PDGF)-α and FGFR4 [178][179][180]. Some of these tumors express androgen receptors and produce CA-125 [181,182]. Approximately a third of DSRCTs express c-Kit [181].…”

Section: Molecular Pathology and Geneticsmentioning

confidence: 99%

Adult human sarcomas. I. Basic science

Sinkovics¹

2007

Expert Review of Anticancer Therapy

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“…Another attempt at developing treatments for this disease was the use of a novel molecularly targeted therapy and a new chemical agent (15). We examined the expression of c-kit, androgen receptor, CD20 and epidermal growth factor receptor using a biopsy sample (16,17). However, we found that none of the markers were expressed in tumor cells; therefore, we could not use any molecularly targeted agent in this case.…”

Section: Discussionmentioning

confidence: 99%

A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy

et al. 2011

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Abstract. Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive and malignant tumor that predominantly affects young males. No standard therapy is currently available for patients with DSRCT and the prognosis remains extremely poor. In this study, we report a thought-provoking DSRCT case. A 24-year-old male was admitted to our hospital with a chief complaint of hematemesis. Computed tomography revealed a retrovesical mass with a splenic hilar tumor, multiple lung and liver tumors and marked lymph node swellings. The source of hematemesis was gastric varices caused by the compression of the splenic vein by a splenic hilar tumor. The patient was provided with a histological diagnosis of DSRCT based on needle biopsy from the liver tumors and the pelvic mass was thought to be the primary lesion. This is a long-term survival case of metastatic DSRCT treated with multimodal therapy including 15 courses of multiagent chemotherapy, radiation therapy for the hepatic portal region using 42.5 Gy, and four instances of therapeutic endoscopy. The prolonged progression-free survival period (15 months) obtained following chemotherapy suggests the chemosensitive feature of the disease. We used a modified P6 regimen (cyclophosphamide, pirarubicin, vincristine, ifosfamide and etoposide) and a modified PAVEP regimen (cyclophosphamide, pirarubicin, etoposide and cisplatin) to decrease severe adverse events and to improve the completion rate of chemotherapy. DSRCT is an aggressive but chemo-sensitive disease, and continuous chemotherapy using an appropriate regimen with possible supportive care is essential for long-term survival. This case report may represent a treatment option for this rare disease.

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“…The reason for male preponderance is unknown. In one study androgen receptors were present in 10/27 (37%; P = 0.0045) [10].…”

Section: Introductionmentioning

confidence: 96%

“…The general pattern of treatment failure is recurrent disease first in the peritoneal cavity, then in the liver, and finally in distant sites. Patients typically are young (ages 5-30 years) at presentation and 80-90% are males [3,[8][9][10][11]. The reason for male preponderance is unknown.…”

Section: Introductionmentioning

confidence: 99%

Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

Hayes‐Jordan

Anderson

2009

Oncol Rev

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Desmoplastic small round cell tumor (DSRCT) is a very rare disease of children, adolescents, and young adults and involves the abdominal cavity. DSRCT has characteristic fusion gene involving EWS1 and WT1 translocation, t(11;22)(p13;q12). Unlike Ewing's sarcoma of bone, DSRCT usually presents with diffuse peritoneal implants that are prone to recur. The primary organ of origin of DSRCT is mesenchyme of the peritoneum. This makes it a very unique tumor that is difficult to treat because of the infiltrative and diffuse nature of the peritoneum. The challenge of local control is to remove dozens to hundreds of tumors studding the peritoneal cavity, and then eliminate microscopic disease. We review a sequential multimodality strategy to reduce macroscopic and microscopic disease including neoadjuvant chemotherapy, aggressive surgery including an emerging new therapy to use after surgery to treat microscopic residual disease: continuous hyperthermic peritoneal chemotherapy, then radiation and adjuvant chemotherapy.

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Androgen and c-Kit receptors in desmoplastic small round cell tumors resistant to chemotherapy: novel targets for therapy

Cited by 43 publications

References 33 publications

Adult human sarcomas. I. Basic science

Adult human sarcomas. I. Basic science

A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy

Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

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