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Home NEWS Science News Cancer

Genetic “Trojan Horse” Targets and Destroys Cancer Cells Associated with Kaposi’s Sarcoma

Bioengineer by Bioengineer
October 1, 2025
in Cancer
Reading Time: 4 mins read
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Genetic “Trojan Horse” Targets and Destroys Cancer Cells Associated with Kaposi’s Sarcoma
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In a groundbreaking advancement poised to redefine cancer treatment paradigms, researchers at the UC Davis Comprehensive Cancer Center have unveiled a revolutionary gene therapy that selectively targets cancers associated with the Kaposi’s sarcoma-associated herpesvirus (KSHV). This herpesvirus, notorious for its oncogenic capacity, is primarily implicated in Kaposi’s sarcoma—a cancer that severely affects immunocompromised patients, especially those with HIV/AIDS in regions such as sub-Saharan Africa. By leveraging a sophisticated gene therapy vector that discriminates between infected and healthy cells, the scientists aim to eradicate malignant cells with unprecedented precision while mitigating the collateral damage often seen in conventional therapies.

The innovative therapeutic approach employs an adeno-associated virus (AAV), a benign vector sophisticatedly engineered to infiltrate only KSHV-infected cancer cells. The selectivity exploits a unique viral protein, LANA, which is exclusively expressed in cells harboring this oncogenic herpesvirus. Upon infection, the therapy activates, manufacturing a modified thymidine kinase enzyme within these compromised cells. This enzyme then metabolizes ganciclovir—an antiviral drug traditionally used against herpesviruses—transforming it into a potent cytotoxic agent that triggers the destruction of the infected cancer cells. This precision-guided mechanism resembles a molecular Trojan horse, siphoning the virus’s own biology to instruct self-destruction selectively within malignancies.

Lead researcher Professor Yoshihiro Izumiya and his team carried out extensive preclinical assessments employing both human cell cultures and murine models emulating KSHV-related tumors. Their studies demonstrated that tumors subjected to this gene therapy, in tandem with ganciclovir administration, exhibited dramatic growth arrest and regression, affirming the approach’s therapeutic efficacy. Intriguingly, the treatment was devoid of detectable adverse effects in the animal models, underscoring a safety profile that surpasses many existing anticancer regimens where systemic toxicity remains a formidable hurdle. This aspect accentuates the therapy’s translational potential for immunocompromised and vulnerable populations.

At the molecular level, the mechanism’s elegance lies in its reliance on LANA—a latency-associated nuclear antigen integral to KSHV’s lifecycle and oncogenic persistence. Since LANA is absent in uninfected cells, the gene therapy’s activation is confined, ensuring that non-malignant tissue is spared. This refined specificity counters the broad cytotoxicity induced by chemotherapy and radiation, signaling a transformative step towards precision oncology. Moreover, the system’s modular design suggests that similar strategies could be tailored for other virus-driven cancers, expanding the therapeutic arsenal against virally induced tumors.

The research also delved into synergistic treatment methodologies. The team observed that certain anticancer agents capable of reactivating latent KSHV enhanced the gene therapy’s efficacy by amplifying the expression of viral markers like LANA. This reactivation strategy effectively increases the therapeutic vector’s activation window, allowing a more robust penetration and elimination of the infected cancer cells. Such combinatorial regimens may optimize clinical outcomes and reduce the likelihood of resistance development.

Kaposi’s sarcoma, historically a devastating diagnosis with limited treatment options, particularly in resource-poor settings, stands to benefit immensely from these findings. Conventional treatments often entail systemic chemotherapy with substantial side effect profiles and variable efficacy, especially in patients with compromised immunity. The gene therapy’s precision and low toxicity offer a promising alternative that can extend survival and improve quality of life without the burden of debilitating side effects.

Notably, KSHV is implicated not just in Kaposi’s sarcoma but also in several rare yet aggressive lymphomas, including primary effusion lymphoma and multicentric Castleman disease. These cancers are notoriously difficult to treat due to their complex pathogenesis and the patients’ immunological vulnerabilities. The selective gene therapy approach unveiled by UC Davis scientists may pave a new path in tackling these malignancies by eradicating the viral reservoirs sustaining tumor growth.

Despite these promising preclinical results, the researchers emphasize that human trials remain further down the developmental pipeline. Rigorous investigations into dosage optimization, delivery methods, long-term safety, and efficacy are necessary before clinical implementation. However, the compelling nature of the results fuels optimism for a near future where personalization of cancer therapy—especially for virally induced cancers—becomes mainstream.

This trailblazing study opens doors to harnessing the viral biology of oncogenic viruses as therapeutic vulnerabilities. By redirecting the virus’s molecular machinery against itself, the therapy exemplifies a paradigm shift from nonspecific cytotoxic treatments to smart, virus-tailored interventions. The use of adeno-associated viruses as delivery vehicles further exemplifies the remarkable potential of gene therapy platforms in the fight against cancer.

The implications of this research transcend the immediate scope of KSHV-related cancers. It highlights how understanding the intricate virus-host dynamics can be translated into clinical innovations. As researchers continue to dissect the genomic and proteomic signatures unique to virus-associated tumors, therapies akin to this approach could revolutionize oncological precision medicine, reducing morbidity and reshaping the therapeutic landscape.

Underpinning this breakthrough are the meticulous efforts by Professor Izumiya’s interdisciplinary team at the UC Davis Department of Biochemistry and Molecular Medicine and the Department of Dermatology. Their collaborative work, funded by the National Cancer Institute and the American Cancer Society, underscores the critical importance of sustained investment in fundamental and translational research to combat cancer’s evolving challenges.

The findings, detailed in the upcoming December issue of Molecular Therapy Oncology, mark a substantial leap forward. They beckon a future where cancer treatment is not only guided by the tumor’s genetic makeup but also by the infectious agents that drive oncogenesis. This dual-faceted approach promises to transform clinical care paradigms for some of the most challenging cancers worldwide.

For patients, clinicians, and researchers alike, this gene therapy represents a beacon of hope—a therapeutic innovation marrying viral biology intricacy with cutting-edge gene editing technologies. Its successful transition from laboratory models to clinical settings could usher in a new era of personalized, effective, and safe treatment modalities against KSHV-associated malignancies and beyond.

Subject of Research: Gene Therapy for Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-Associated Cancers

Article Title: Design, development, and evaluation of gene therapeutics specific to KSHV-associated diseases

News Publication Date: 18-Dec-2025

Web References:

UC Davis Comprehensive Cancer Center: https://health.ucdavis.edu/cancer/
Kaposi’s Sarcoma Information: https://www.cancer.org/cancer/types/kaposi-sarcoma/about/what-is-kaposi-sarcoma.html
Molecular Therapy Oncology Journal: https://www.cell.com/molecular-therapy-family/oncology/home
Full Research Article: https://www.cell.com/molecular-therapy-family/oncology/fulltext/S2950-3299(25)00119-5

References:
Izumiya, Y., et al. (2025). Design, development, and evaluation of gene therapeutics specific to KSHV-associated diseases. Molecular Therapy Oncology, [DOI: 10.1016/j.omton.2025.201050].

Keywords:
Kaposi’s Sarcoma, KSHV, Gene Therapy, Adeno-Associated Virus, Thymidine Kinase, Ganciclovir, Viral Oncology, Precision Medicine, Cancer Therapeutics, Latent Viral Infection, Immunocompromised Patients, Targeted Cancer Therapy

Tags: adeno-associated virus therapycytotoxic agents for cancer treatmentgene therapy for Kaposi’s sarcomaHIV/AIDS and cancerimmunocompromised cancer patientsinnovative cancer therapiesKSHV cancer treatmentprecision medicine in oncologyselective cancer cell targetingTrojan horse gene therapyUC Davis Comprehensive Cancer Center researchviral protein LANA in cancer

Tags: adeno-associated virus vectorKaposi’s sarcoma gene therapyKSHV-targeted treatmentprecision oncology innovationsTrojan horse cancer therapy
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