Targets for cancer therapy in childhood sarcomas

Wachtel, Marco; Schäfer, Beat W.

doi:10.1016/j.ctrv.2010.02.007

Cited by 96 publications

(60 citation statements)

References 176 publications

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“…The improvement in survival was closely related to rapid disease recognition and advances in applying surgery, radiotherapy, multi‐drug, multi‐cycle adjuvant chemotherapy regimes 11, 22. However, there was little progress in improving the survival of osteosarcoma in the three decades despite the multi‐modal approach, and treatment is accompanied by many early and late side effects 23, 24. This highlights the urgency of developing novel and more specific therapeutic approaches to improve the outcome of osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Increased survival of patients aged 0‐29 years with osteosarcoma: A period analysis, 1984‐2013

Sun

et al. 2018

Cancer Medicine

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PurposeOsteosarcoma is the most common primary malignancy of bone, and typically occurs among children and adolescence. This study aims to evaluate treatment outcomes among children, adolescents and young adults with osteosarcoma over the three decades by the changes in the long‐term relative survival.MethodsOsteosarcoma incidence and relative survival data from Surveillance, Epidemiology, and End Results (SEER) registries during 1984‐2013 were analyzed. The survival differences over three decades, age, sex, race, and socioeconomic status (SES) were assessed by comparing Kaplan‐Meier curves.ResultsThe overall incidence of osteosarcoma kept relatively stable with 0.4 per 100 000 in the three decades with the peak incidence occurring in the aged 10‐19 group. The 10‐year relative survival rate (RSR) increased from 57.7% to 61.0% in the three decades, with the greatest increase in the aged 0‐9 group from 48.2% to 65.7%. The 10‐year RSR improved from 54.1% to 61.5% in males, and from 62.4% to 63.0% in females, respectively, in the three decades. Furthermore, survival dramatically improved from 30% to 60% in the high‐poverty group over the three decades.ConclusionThis study demonstrated that the overall incidence of osteosarcoma remained stable, with an improvement in survival in the three decades. The improved survival was greater in males than in females in the three decades. Furthermore, the survival significantly increased in high‐poverty group, which was attributed to increasing improved health care system and patients with low finance can also have access to receiving effective and consistent treatment without distinction.

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Section: Discussionmentioning

confidence: 99%

Increased survival of patients aged 0‐29 years with osteosarcoma: A period analysis, 1984‐2013

Sun

et al. 2018

Cancer Medicine

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“…Relationship between survivin expression and RMS are still unknown. However, some antiapoptotic activities were detected in RMS (38,39). Survivin was strongly overexpressed in both alveolar and embryonal RMS cell lines and in RMS biopsy specimens (40).…”

Section: Discussionmentioning

confidence: 99%

Survivin selective inhibitor YM155 promotes cisplatin-induced apoptosis in embryonal rhabdomyosarcoma

Ueno

Uehara

Nakahata

et al. 2016

International Journal of Oncology

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Abstract. Survivin, a member of the inhibitor of apoptosis protein family, functions as a key regulator of programmed cell death. YM155 is a small molecule that selectively inhibits survivin. We investigated the effect of YM155 on survivin suppression in the human rhabdomyosarcoma (RMS) cell line RD. The efficacy of YM155 in combination with cisplatin was also determined in a xenograft model. The effect of YM155 on survivin expression in the RD cell line was examined at both mRNA and protein levels using real-time PCR and western blot analysis. RD cells were cultured with various concentrations of YM155, then cisplatin was added to the medium and the anti-proliferation response was determined. Cell growth was evaluated by WST-8 assay. Finally, the efficacy of YM155 combined with cisplatin was examined in an established xenograft model. Survivin mRNA levels in the RD cell line were decreased to 72 and 24% at 24 and 48 h, respectively, after 10 nM of YM155 was added. YM155 also decreased the levels of survivin protein. YM155 treatment (10 nM) inhibited cell proliferation of RD in a dose-dependent manner in vitro, with 58% of cells viable at 48 h. When cultured with 10 nM of YM155 and 10 µM cisplatin, RD cells demonstrated only 25% of the growth observed when cultured with cisplatin alone. YM155 in combination with cisplatin significantly inhibited tumor growth by 13% compared with control (P<0.0001) in RD xenograft tumors. YM155 increased the sensitivity of cisplatin by suppressing survivin in the embryonal RMS cell line RD. Further studies should investigate the use of YM155 as an apoptosis inducer, either alone or in combination with cisplatin, for the treatment of malignant RMS.

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“…129 Currently, the main molecular targets under investigation to improve therapies for advanced, recurrent and metastatic RMS include receptors (IGF-1R, c-Met, PDGFR,c-Kit), intracellular signaling molecules (mTOR, MEK/ERK), cell cycle (CDK4/CDK6) and apoptotic proteins (p53, Bcl-2, TRAIL), the proteasome machinery, HSP90, histone deacetylases, angiogenetic molecules (VEGFR, VEGF), and the Pax3-Foxo1 oncoprotein (all these targets have already been extensively discussed in ref. 130 ). While preclinical in vitro and in vivo studies have suggested the effectiveness of inhibitors targeting RTK like IGF-1R and PDGF-R, 131 and pathways like the AKTmTOR, results from recently published clinical trials have indicated that these therapies are not sufficient to improve the outcome in patients with recurrent disease (Table 1).…”

Section: Targeting Intratumor Cell Heterogeneity: a Difficult But Promentioning

confidence: 99%

Uncovering metabolism in rhabdomyosarcoma

Monti

Fanzani

2016

Cell Cycle

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Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes five different histotypes, with two most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies two major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signalling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the “state of art” of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies

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Targets for cancer therapy in childhood sarcomas

Cited by 96 publications

References 176 publications

Increased survival of patients aged 0‐29 years with osteosarcoma: A period analysis, 1984‐2013

Increased survival of patients aged 0‐29 years with osteosarcoma: A period analysis, 1984‐2013

Survivin selective inhibitor YM155 promotes cisplatin-induced apoptosis in embryonal rhabdomyosarcoma

Uncovering metabolism in rhabdomyosarcoma

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