The molecular mechanisms of virus-induced human cancers

Ameya, Gemechu; Birri, Dagim Jirata

doi:10.1016/j.micpath.2023.106292

Cited by 8 publications

(2 citation statements)

References 132 publications

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“…Moreover, other virally induced tumors such as hepatitis B-induced hepatic carcinoma, human herpes virus 8 (HHV-8)-induced Kaposi’s sarcoma, and human papillomavirus (HPV)-induced cervical carcinoma [ 81 , 82 ] are all potential treatment models for lytic-induced tumoricidal therapy by NEO212. In each instance, infection of the host cell not only serves to induce tumorigenesis but also to shield the virus from antiviral therapy.…”

Section: Discussionmentioning

confidence: 99%

Activation of Epstein–Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide

Hartman-Houstman,

Swenson,

Minea

et al. 2024

Cancers

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The Epstein–Barr virus (EBV) is accepted as a primary risk factor for certain nasopharyngeal carcinoma (NPC) subtypes, where the virus persists in a latent stage which is thought to contribute to tumorigenesis. Current treatments are sub-optimal, and recurrence occurs in many cases. An alternative therapeutic concept is aimed at triggering the lytic cycle of EBV selectively in tumor cells as a means to add clinical benefit. While compounds able to stimulate the lytic cascade have been identified, their clinical application so far has been limited. We are developing a novel anticancer molecule, NEO212, that was generated by covalent conjugation of the alkylating agent temozolomide (TMZ) to the naturally occurring monoterpene perillyl alcohol (POH). In the current study, we investigated its potential to trigger the lytic cycle of EBV in NPC cells in vitro and in vivo. We used the established C666.1 cell line and primary patient cells derived from the brain metastasis of a patient with NPC, both of which harbored latent EBV. Upon treatment with NEO212, there was an increase in EBV proteins Zta and Ea-D, key markers of the lytic cycle, along with increased levels of CCAAT/enhancer-binding protein homologous protein (CHOP), a marker of endoplasmic reticulum (ER) stress, followed by the activation of caspases. These effects could also be confirmed in tumor tissue from mice implanted with C666.1 cells. Towards a mechanistic understanding of these events, we used siRNA-mediated knockdown of CHOP and inclusion of anti-oxidant compounds. Both approaches blocked lytic cycle induction by NEO212. Therefore, we established a sequence of events, where NEO212 caused reactive oxygen species (ROS) production, which triggered ER stress and elevated the levels of CHOP, which was required to stimulate the lytic cascade of EBV. Inclusion of the antiviral agent ganciclovir synergistically enhanced the cytotoxic impact of NEO212, pointing to a potential combination treatment for EBV-positive cancers which should be explored further. Overall, our study establishes NEO212 as a novel agent able to stimulate EBV’s lytic cycle in NPC tumors, with implications for other virus-associated cancers.

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Section: Discussionmentioning

confidence: 99%

Activation of Epstein–Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide

Hartman-Houstman,

Swenson,

Minea

et al. 2024

Cancers

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“…As a consequence of its natural viral activity, transcription regulation studies have shown that the Tat-1 protein has the potential to alter host gene expression quite profoundly [139]. It has been found that Tat-1 has a pleiotropic effect in numerous cell types, displaying growth-promoting activity, angiogenic and anti-apoptotic functions [140], which all promote and support the hallmarks of cancer [126] (Figure 1). It achieves these functions by acting as a broad-range transcription factor to induce the expression of growth factors, cytokines, cytokine receptors and other transcription factors that aid in the replication of HIV.…”

Section: Role Of Hiv-1 Tat-1 Protein In Cancer Developmentmentioning

confidence: 99%

Cancer and HIV: The Molecular Mechanisms of the Deadly Duo

Omar,

Marques,

Crawford

2024

Cancers

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The immune deficiency associated with human immunodeficiency virus (HIV) infection causes a distinct increased risk of developing certain cancer types. Kaposi sarcoma (KS), invasive cervical cancer and non-Hodgkin’s lymphoma (NHL) are the prominent malignancies that manifest as a result of opportunistic viral infections in patients with advanced HIV infection. Despite the implementation of antiretroviral therapy (ART), the prevalence of these acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) remains high in developing countries. In contrast, developed countries have experienced a steady decline in the occurrence of these cancer types. However, there has been an increased mortality rate attributed to non-ADMs. Here, we provide a review of the molecular mechanisms that are responsible for the development of ADMs and non-ADMs which occur in HIV-infected individuals. It is evident that ART alone is not sufficient to fully mitigate the potential for ADMs and non-ADMs in HIV-infected individuals. To enhance the diagnosis and treatment of both HIV and malignancies, a thorough comprehension of the mechanisms driving the development of such cancers is imperative.

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The Genomics Evolutionary of Cancer-Associated Pathogens

Velázquez-Márquez,

Núñez-Farfán

2024

Pathogens Associated With the Development of Cancer in Humans

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The molecular mechanisms of virus-induced human cancers

Cited by 8 publications

References 132 publications

Activation of Epstein–Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide

Activation of Epstein–Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide

Cancer and HIV: The Molecular Mechanisms of the Deadly Duo

The Genomics Evolutionary of Cancer-Associated Pathogens

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