Therapeutic options for human herpesvirus-8/Kaposi’s sarcoma-associated herpesvirus-related disorders

Aoki, Yoshiyasu; Tosato, Giovanna

doi:10.1586/14787210.2.2.213

Cited by 11 publications

(4 citation statements)

References 117 publications

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“…Currently there is no efficient treatment for PEL, and the treatment modalities in use consist mostly of cytostatic drugs with DNA-damaging activities, which are neither potent nor selective for this malignancy (reviewed in ref. 21). The highly…”

Section: Discussionmentioning

confidence: 99%

“…Despite some interesting new therapeutic leads such as inhibition of NF-κB signaling (18,19) or RNA interference against viral latent proteins (20), the current clinical treatments based on high-dose chemotherapy regimens are neither potent nor selective for this cancer (21,22), and PEL remains a fatal disease. Although p53 mutations are relatively common in hematopoietic malignancies, the majority of the PELs appear to have WT p53 (23)(24)(25), suggesting that genetic alterations in the p53 gene are not selected for during PEL tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

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Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas

Sarek¹,

Kurki²,

Enbäck³

et al. 2007

J. Clin. Invest.

133

135

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Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent for primary effusion lymphoma (PEL), a nonHodgkin type lymphoma manifesting as an effusion malignancy in the affected individual. Although KSHV has been recognized as a tumor virus for over a decade, the pathways for its tumorigenic conversion are incompletely understood, which has greatly hampered the development of efficient therapies for KSHV-induced malignancies like PEL and Kaposi's sarcoma. There are no current therapies effective against the aggressive, KSHV-induced PEL. Here we demonstrate that activation of the p53 pathway using murine double minute 2 (MDM2) inhibitor Nutlin-3a conveyed specific and highly potent activation of PEL cell killing. Our results demonstrated that the KSHV latency-associated nuclear antigen (LANA) bound to both p53 and MDM2 and that the MDM2 inhibitor Nutlin-3a disrupted the p53-MDM2-LANA complex and selectively induced massive apoptosis in PEL cells. Together with our results indicating that KSHV-infection activated DNA damage signaling, these findings contribute to the specificity of the cytotoxic effects of Nutlin-3a in KSHV-infected cells. Moreover, we showed that Nutlin-3a had striking antitumor activity in vivo in a mouse xenograft model. Our results therefore present new options for exploiting reactivation of p53 as what we believe to be a novel and highly selective treatment modality for this virally induced lymphoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas

Sarek¹,

Kurki²,

Enbäck³

et al. 2007

J. Clin. Invest.

133

135

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“…The objective for the management of KS is to manage the symptoms as treatment is often not curative, and prognosis depends on the disease severity at presentation [27]. Patients with systemic disseminated KS, as in our case, require systemic chemotherapy [28]. The clinical manifestations of KS following significant immunosuppression generally resolve, in most cases, when the immunosuppressive therapy is changed, reduced, or discontinued [5].…”

Section: Discussionmentioning

confidence: 91%

Oral–visceral iatrogenic Kaposi sarcoma following treatment for acute lymphoblastic leukemia: a case report and review of the literature

et al. 2022

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Background There have hardly been any reported cases of children presenting with Kaposi sarcoma as a second malignancy following treatment for acute lymphoblastic leukemia outside a transplant setting. Case presentation We report a case of a 5-year-old boy of Bantu origin, which, to our knowledge, could be only the second reported case of oral–visceral Kaposi sarcoma after acute lymphoblastic leukemia treatment. The patient presented with a 1-month history of progressive, non-painful, soft tissue oral mass, 1 month after completing treatment for high-risk acute lymphoblastic leukemia. He was successfully treated for Kaposi sarcoma on a two-drug regimen (bleomycin and vincristine) with good clinical response. Conclusion Visceral Kaposi sarcoma as a second malignancy may occur after pediatric acute lymphoblastic leukemia treatment, but its rarity makes it unlikely to raise suspicion among clinicians, thus precluding early diagnosis and treatment. We recommend routine evaluation for Kaposi sarcoma lesions in children undergoing long-term surveillance following treatment for childhood acute leukemia.

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“…In another clinical study, DNMT inhibitor azacytidine ( Table 1) initiated viral gene re-expression in EBV linked tumors (Chan et al, 2004). While these inhibitors are promising candidates as the therapeutics to control of herpesviral infections (Figure 1), the possibilities of reactivation and status of co-infection with other (Schang et al, 2002;Kudoh et al, 2004;Taylor et al, 2004;Shin et al, 2008) Purvalanol A HSV, VZV and EBV (Schang et al, 2002;Kudoh et al, 2004;Moffat et al, 2004) Olomoucine II HSV and HCMV (Moffat et al, 2004) Indirubin-3'-monoxime HCMV GSK3b (Hertel et al, 2007 VEGFR tyrosine kinase (Aoki and Tosato, 2004) viruses must be meticulously examined (Ritchie et al, 2009). For example, the usage of suberoylanilide hydroxamic acid (SAHA) or trichostatin A (TSA) ( Table 1) provoked myocarditis through Coxsackievirus B3-induced myocardial apoptosis (Zhou et al, 2015).…”

Section: Epigenetic Targeted Therapymentioning

confidence: 99%

Targeting Host Cellular Factors as a Strategy of Therapeutic Intervention for Herpesvirus Infections

Asha

Sharma-Walia

2021

Front. Cell. Infect. Microbiol.

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Herpesviruses utilize various host factors to establish latent infection, survival, and spread disease in the host. These factors include host cellular machinery, host proteins, gene expression, multiple transcription factors, cellular signal pathways, immune cell activation, transcription factors, cytokines, angiogenesis, invasion, and factors promoting metastasis. The knowledge and understanding of host genes, protein products, and biochemical pathways lead to discovering safe and effective antivirals to prevent viral reactivation and spread infection. Here, we focus on the contribution of pro-inflammatory, anti-inflammatory, and resolution lipid metabolites of the arachidonic acid (AA) pathway in the lifecycle of herpesvirus infections. We discuss how various herpesviruses utilize these lipid pathways to their advantage and how we target them to combat herpesvirus infection. We also summarize recent development in anti-herpesvirus therapeutics and new strategies proposed or under clinical trials. These anti-herpesvirus therapeutics include inhibitors blocking viral life cycle events, engineered anticancer agents, epigenome influencing factors, immunomodulators, and therapeutic compounds from natural extracts.

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Therapeutic options for human herpesvirus-8/Kaposi’s sarcoma-associated herpesvirus-related disorders

Cited by 11 publications

References 117 publications

Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas

Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas

Oral–visceral iatrogenic Kaposi sarcoma following treatment for acute lymphoblastic leukemia: a case report and review of the literature

Targeting Host Cellular Factors as a Strategy of Therapeutic Intervention for Herpesvirus Infections

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