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The tumor suppressor gene RIZ in cancer gene therapy (review)
Richard Canote1, Yong Du, Tobias Carling
1Dcantix, Inc., San Diego, CA 92130, USA.
Abstract:
In recent years, significant progress has been made in understanding the nature of the human genome and the role that genes and their related proteins play in both normal and diseased cells. It has been proven that many cancers are caused by the mutation of certain genes or lack of gene function. The introduction of those genes into cancer cells where gene function is compromised, can work to restore gene function and stop tumor progression. There have been numerous clinical trials, which have shown that gene therapy products are efficacious in humans. The RIZ1 gene is a member of a superfamily of histone/protein methyltransferases. The gene is commonly inactivated in human cancers. Gene knock-out study has established RIZ1 as a tumor susceptibility gene in mice. The gene has potent tumor suppressive activities in causing apoptosis, G2/M arrest, or both. Preclinical animal studies have shown that a recombinant adenovirus expressing the gene, AdRIZ1, can suppress the growth of colon cancer xenografts. Therefore, AdRIZ1 shows promise as a new generation of gene therapy products to enter the clinic.
Insights
Gene therapy using AdRIZ1 shows promise for treating cancer by restoring the tumor-suppressive RIZ1 gene function. This approach aims to halt tumor progression in patients with compromised gene function.
Area of Science:
- Genetics and Genomics
- Cancer Biology
- Molecular Medicine
Background:
- Gene mutations and loss of function are key drivers of cancer development.
- Gene therapy offers a potential strategy to restore normal gene function and inhibit tumor growth.
- The RIZ1 gene, a histone/protein methyltransferase, is frequently inactivated in human cancers.
Purpose of the Study:
- To evaluate the therapeutic potential of the RIZ1 gene in cancer treatment.
- To assess the efficacy of a recombinant adenovirus carrying the RIZ1 gene (AdRIZ1) in preclinical cancer models.
Main Methods:
- Gene knock-out studies in mice to establish RIZ1's tumor suppressive role.
- Preclinical studies using a recombinant adenovirus expressing RIZ1 (AdRIZ1).
- Administration of AdRIZ1 to colon cancer xenografts in animal models.
Main Results:
- RIZ1 gene inactivation is common in human cancers.
- RIZ1 exhibits potent tumor suppressive activities, including apoptosis and G2/M cell cycle arrest.
- AdRIZ1 significantly suppressed the growth of colon cancer xenografts in animal studies.
Conclusions:
- The RIZ1 gene is a critical tumor suppressor.
- AdRIZ1 demonstrates significant potential as a gene therapy agent for colon cancer.
- AdRIZ1 represents a promising new candidate for clinical gene therapy applications in oncology.