Abstract
A multidisciplinary approach of combining surgery, chemotherapy and radiotherapy has remained the accepted standard management for various types of human cancer. However, many new treatment options have recently become available, including molecular targeted therapies, immunotherapies and oncolytic virotherapies. Replication-selective tu-mor-specific viruses have been designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. We constructed an attenuated adenovirus 5 vector, telomelysin (OBP-301), in which the telomerase-specific promoter drives expression of viral replication-inducible E1 genes. Although telomelysin alone exhibited substantial antitumor effects both in animal models and in clinical trials, telomelysin has the potential to be the first-in-class oncolytic virus for combination therapy based on our current understanding of the molecular mechanisms. Telomelysin sensitizes human cancer cells to ionizing radiation by inhibiting the radiation-induced DNA repair machinery, and also eliminates radio-resistant quiescent cancer stem-like cells by promoting cell cycle entry. A clinical trial of intratumoral administration of telomelysin with radiotherapy in esophageal cancer patients is currently underway. This article reviews recent highlights in the rapidly evolving field of multidisciplinary therapy with telomelysin.
| Original language | English |
|---|---|
| Pages (from-to) | 178-187 |
| Number of pages | 10 |
| Journal | Current Cancer Therapy Reviews |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jan 1 2015 |
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Keywords
- Adenovirus
- Cancer stem cells
- DNA repair
- Radiotherapy
- Telomerase
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Cancer Research
Cite this
Multidisciplinary cancer therapy with telomerase-specific oncolytic adenovirus. / Fujiwara, Toshiyoshi; Kagawa, Shunsuke; Tazawa, Hiroshi.
In: Current Cancer Therapy Reviews, Vol. 11, No. 3, 01.01.2015, p. 178-187.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multidisciplinary cancer therapy with telomerase-specific oncolytic adenovirus
AU - Fujiwara, Toshiyoshi
AU - Kagawa, Shunsuke
AU - Tazawa, Hiroshi
PY - 2015/1/1
Y1 - 2015/1/1
N2 - A multidisciplinary approach of combining surgery, chemotherapy and radiotherapy has remained the accepted standard management for various types of human cancer. However, many new treatment options have recently become available, including molecular targeted therapies, immunotherapies and oncolytic virotherapies. Replication-selective tu-mor-specific viruses have been designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. We constructed an attenuated adenovirus 5 vector, telomelysin (OBP-301), in which the telomerase-specific promoter drives expression of viral replication-inducible E1 genes. Although telomelysin alone exhibited substantial antitumor effects both in animal models and in clinical trials, telomelysin has the potential to be the first-in-class oncolytic virus for combination therapy based on our current understanding of the molecular mechanisms. Telomelysin sensitizes human cancer cells to ionizing radiation by inhibiting the radiation-induced DNA repair machinery, and also eliminates radio-resistant quiescent cancer stem-like cells by promoting cell cycle entry. A clinical trial of intratumoral administration of telomelysin with radiotherapy in esophageal cancer patients is currently underway. This article reviews recent highlights in the rapidly evolving field of multidisciplinary therapy with telomelysin.
AB - A multidisciplinary approach of combining surgery, chemotherapy and radiotherapy has remained the accepted standard management for various types of human cancer. However, many new treatment options have recently become available, including molecular targeted therapies, immunotherapies and oncolytic virotherapies. Replication-selective tu-mor-specific viruses have been designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. We constructed an attenuated adenovirus 5 vector, telomelysin (OBP-301), in which the telomerase-specific promoter drives expression of viral replication-inducible E1 genes. Although telomelysin alone exhibited substantial antitumor effects both in animal models and in clinical trials, telomelysin has the potential to be the first-in-class oncolytic virus for combination therapy based on our current understanding of the molecular mechanisms. Telomelysin sensitizes human cancer cells to ionizing radiation by inhibiting the radiation-induced DNA repair machinery, and also eliminates radio-resistant quiescent cancer stem-like cells by promoting cell cycle entry. A clinical trial of intratumoral administration of telomelysin with radiotherapy in esophageal cancer patients is currently underway. This article reviews recent highlights in the rapidly evolving field of multidisciplinary therapy with telomelysin.
KW - Adenovirus
KW - Cancer stem cells
KW - DNA repair
KW - Radiotherapy
KW - Telomerase
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UR - http://www.scopus.com/inward/citedby.url?scp=85047184316&partnerID=8YFLogxK
U2 - 10.2174/1573394712666160128201822
DO - 10.2174/1573394712666160128201822
M3 - Article
VL - 11
SP - 178
EP - 187
JO - Current Cancer Therapy Reviews
JF - Current Cancer Therapy Reviews
SN - 1573-3947
IS - 3
ER -