Targeted therapy in sarcomas other than GIST tumors

Sborov, Douglas W.; Chen, James L.

doi:10.1002/jso.23802

Cited by 12 publications

(17 citation statements)

References 93 publications

(118 reference statements)

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“…The effect of chemotherapy in LMS and SRC, not amenable to treatment with imatinib, is still uncertain and controversial. 9,10 In the current study, 57.4% of patients with LMS and 56% of patients with SRC received some form of perioperative chemotherapy. We did not see the same survival benefit from chemotherapy in patients with LMS and SRC that we saw from imatinib in patients with GIST (data not shown).…”

Section: Discussionmentioning

confidence: 78%

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Survival After Resection of Gastrointestinal Stromal Tumor and Sarcoma Liver Metastases in 146 Patients

Brudvik

Patel

Roland

et al. 2015

Journal of Gastrointestinal Surgery

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Background We investigated outcomes by primary tumor type in patients who underwent resection of liver metastases from gastrointestinal stromal tumors (GIST), leiomyosarcomas, and other sarcomas. Method Our institutional liver database was used to identify patients who underwent resection from 1998 through 2013. Histopathological, clinical, and survival data were analyzed. Results One hundred forty-six patients underwent resection of liver metastases from GIST (n=49), leiomyosarcomas (n=47), or other sarcomas (n=50). The 5-year overall survival (OS) rates in patients with GIST, leiomyosarcomas, and other sarcomas were 55.3%, 48.4%, and 44.9%, respectively, and the 10-year OS rates were 52.5%, 9.2%, and 23.0%, respectively. The 5-year recurrence-free survival (RFS) rate was better for GIST (35.7%; p=0.003) than for leiomyosarcomas (3.4%) and other sarcomas (21.4%). Lung recurrence was more common for leiomyosarcomas (36% of patients; p<0.0001) than for other sarcomas (12%) and GIST (2%). For GIST, the findings support a benefit of imatinib regarding the 5-year RFS rate compared to resection alone (47.1% vs 9.5%; p=0.013). For leiomyosarcoma, primary tumor location did not affect the 5-year RFS rate (intraabdominal 14.5%; other location 0%; p=0.182). Conclusion Liver metastases from GIST, leiomyosarcomas, and other sarcomas should be assessed separately as their survival and recurrence patterns are different. This is especially important for GIST, for which imatinib is now available.

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Section: Discussionmentioning

confidence: 78%

“…This problem became especially important after the introduction of imatinib mesylate (imatinib) for treatment of GIST because imatinib has improved outcomes significantly for patients with GIST whereas targeted therapy for LMS remains experimental and LMS respond poorly to chemotherapy. 9,10 …”

Section: Introductionmentioning

confidence: 99%

Survival After Resection of Gastrointestinal Stromal Tumor and Sarcoma Liver Metastases in 146 Patients

Brudvik

Patel

Roland

et al. 2015

Journal of Gastrointestinal Surgery

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“… 16 , 17 Even though localized sarcomas have a high cure rate with surgery, when they recur and/or metastasize they have a poor prognosis with a median survival of approximately 12 months. 18 – 20 …”

Section: Local Control In Sarcomamentioning

confidence: 99%

Managing sarcoma: where have we come from and where are we going?

et al. 2017

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Sarcomas are a heterogeneous group of neoplasms of mesenchymal origin. Approximately 80% arise from soft tissue and 20% originate from bone. To date more than 100 sarcoma subtypes have been identified and they vary in molecular characteristics, pathology, clinical presentation and response to treatment. While sarcomas represent <1% of adult cancers, they account for approximately 21% of paediatric malignancies and thus pose some of the greatest risks of mortality and morbidity in children and young adults. Metastases occur in one-third of all patients and approximately 10–20% of sarcomas recur locally. Surgery in combination with preoperative and postoperative therapies is the primary treatment for localized sarcoma tumours and is the most promising curative possibility. Metastasized sarcomas, on the other hand, are treated primarily with single-agent or combination chemotherapy, but this rarely leads to a complete and robust response and often becomes a palliative form of treatment. The heterogeneity of sarcomas results in variable responses to current generalized treatment strategies. In light of this and the lack of curative strategies for metastatic and unresectable sarcomas, there is a need for novel subtype-specific treatment strategies. With the more recent understanding of the molecular mechanisms underlying the pathogenesis of some of these tumours, the treatment of sarcoma subtypes with targeted therapies is a rapidly evolving field. This review discusses the current management of sarcomas as well as promising new therapies that are currently underway in clinical trials.

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“…Angiogenesis-the formation of new blood vessels-is a well-established property of solid tumors and is essential for their growth and metastasis [1]. Multiple efforts have been made to target this pathway for the treatment of heavily vascularized malignant tumors, however, there has been little success in finding effective treatment options which strengthens the need for novel strategies [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 12,000 new cases of STS per year are seen in the United States, with~50% of patients developing lung metastases, resulting in significant morbidity and mortality [5]. GBM is also a highly vascularized primary brain tumor in adults with extremely poor patient survival rate [2,3]. Therefore, there is an urgent need for novel therapies to improve the survival rate of both STS and GBM [6].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation

Nair

Khosla

Otani

et al. 2020

Cancers

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Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including Imlygic TM , an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angiogenesis inhibition on endothelial cell activation has not been previously described. Here, we tested the effects of Rapid Antiangiogenesis Mediated By Oncolytic Virus (RAMBO), an oHSV which expresses a potent anti-angiogenic gene Vasculostatin on endothelial cell activation in heavily vascularized solid tumors. oHSV treatment induces endothelial cell activation, which inhibits virus propagation and oncolysis in adjacent tumor cells in vitro. Consistently, this was also observed in intravital imaging of intracranial tumor-bearing mice in vivo where infected tumor endothelial cells could efficiently clear the virus without cell lysis. Quantitative real-time PCR (Q-PCR), leukocyte adhesion assay, and fluorescent microscopy imaging data, however, revealed that RAMBO virus significantly decreased expression of endothelial cell activation markers and leukocyte adhesion, which in turn increased virus replication and cytotoxicity in endothelial cells. In vivo RAMBO treatment of subcutaneously implanted sarcoma tumors significantly reduced tumor growth in mice bearing sarcoma compared to rHSVQ. In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.

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Targeted therapy in sarcomas other than GIST tumors

Cited by 12 publications

References 93 publications

Survival After Resection of Gastrointestinal Stromal Tumor and Sarcoma Liver Metastases in 146 Patients

Survival After Resection of Gastrointestinal Stromal Tumor and Sarcoma Liver Metastases in 146 Patients

Managing sarcoma: where have we come from and where are we going?

Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation

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