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Virotherapy as an approach against cancer stem cells
Camilla Ribacka1, Akseli Hemminki
1Cancer Gene Therapy Group, Molecular Cancer Biology Program, University of Helsinki, Helsinki, Finland.
Abstract:
It has been hypothesized that cancers originate from a small population of cells with stem cell-like characteristics, including self-renewal and pluripotency. Such tumor-initiating cells, also referred to as cancer stem cells, are thought to account for relapses following seemingly successful treatments, because their slow turnover and capacity for expelling anti-tumor drugs leaves them untouched by conventional treatment regimens. Targeting of cancer stem cells might be key for improving survival and producing cures in patients with metastatic tumors. Viruses enter cells though infection and might therefore not be sensitive to stem cell resistance mechanisms. During the last decades, oncolytic adenoviruses have been shown to effectively kill cancer cells, by seizing control of their DNA replication machinery and utilizing it for the production of new virions, ultimately resulting in the rupture of the cell. Human safety data in cancer trials has been excellent even when the dose of administered adenovirus has been high. Future approaches include additional modifications of the adenoviral genome that prime them to attack cancer stem cells specifically, utilizing linage-specific cell surface markers, dysfunctional stem cell signaling pathways or up-regulated oncogenic genes. However, already existing oncolytic adenoviruses have displayed potential to efficiently kill not only differentiated cancer cells, but also tumor-initiating stem cells. Here, we review the current literature that supports the existence of cancer stem cells and discuss the potential of virotherapy for killing tumor-initiating cells.
Insights
Cancer stem cells drive tumor relapse. Virotherapy using oncolytic adenoviruses shows promise in targeting and eliminating these resistant cells, potentially improving patient survival.
Area of Science:
- Oncology
- Virology
- Cancer Stem Cell Biology
Background:
- Cancer stem cells (CSCs) are hypothesized to drive tumor initiation, metastasis, and relapse due to their self-renewal and drug-resistance properties.
- Conventional therapies often fail to eradicate CSCs, leading to treatment resistance and disease recurrence.
- Oncolytic viruses, such as adenoviruses, offer a potential therapeutic strategy due to their ability to infect and lyse cancer cells.
Purpose of the Study:
- To review the evidence supporting the existence and role of cancer stem cells in tumor progression.
- To discuss the potential of oncolytic virotherapy, specifically using adenoviruses, as a treatment modality targeting cancer stem cells.
Main Methods:
- Literature review of studies on cancer stem cells and oncolytic adenovirus therapy.
- Analysis of existing data on adenovirus efficacy against cancer cells and potential CSCs.
- Discussion of future strategies for enhancing adenovirus targeting of CSCs.
Main Results:
- Cancer stem cells possess characteristics like self-renewal and drug efflux, contributing to treatment failure.
- Oncolytic adenoviruses demonstrate potent cancer cell killing through viral replication and cell lysis.
- Existing oncolytic adenoviruses show efficacy against both differentiated cancer cells and tumor-initiating stem cells.
Conclusions:
- Cancer stem cells are a critical target for effective cancer treatment and achieving cures.
- Oncolytic adenoviruses represent a promising therapeutic approach with a strong safety profile, capable of targeting CSCs.
- Future research focusing on genetically modified adenoviruses could further enhance their specificity and efficacy against CSCs.
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