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Keywords | Anticancer therapy | oncology | health sciences | virotherapy | pox- | myxoma- | adenovirus | colorectal |<br />
pancreatic | ovarian cancer | tumour-specifi c targeting | spreading | replication | arming | molecular chemotherapy |<br />
non-invasive imaging |<br />
THERADPOX<br />
Optimised and novel oncolytic<br />
adenoviruses and pox viruses in<br />
the treatment of cancer: Virotherapy<br />
combined with molecular chemotherapy<br />
Summary<br />
Today, cancer is the second cause of disease-induced mortality<br />
worldwide. Among the innovative treatments for<br />
cancer, virotherapy holds great promise. Virotherapy exploits<br />
an intrinsic feature of the life cycle of oncolytic viruses (OVs):<br />
replicating and spreading exclusively in tumour cells leading<br />
to their destruction, while not aff ecting normal cells. Clinical<br />
studies have demonstrated the safety and feasibility of this<br />
approach, but have shown only minimal therapeutic effi cacy.<br />
Synergistic eff ects of combination treatments of OVs with<br />
chemo- and radiation therapy have been observed. Nevertheless,<br />
this approach still leaves patients subjected to the<br />
toxic adverse eff ects of chemotherapy and radiation. Thus,<br />
an unmet need exists for the improvement of current and the<br />
development of new treatment platforms, leading to a signifi<br />
cant increase in cure rates.<br />
Owing to their inherent strong oncolytic potency and safety<br />
record, poxvirus and adenovirus-based vectors have been<br />
chosen to pursue the goal of the THERADPOX project: to<br />
improve the safety and therapeutic effi cacy of OVs in vivo.<br />
Novel and improved OVs will be engineered which, in vivo:<br />
• specifi cally target colorectal, pancreatic and ovarian<br />
cancer cells;<br />
• replicate exclusively in cancer cells;<br />
• are armed with therapeutic genes rendering only tumour<br />
cells sensitive to chemotherapy;<br />
• widely spread within the tumour to permit total tumour<br />
eradication.<br />
Through the multidisciplinary work plan proposed and the<br />
strong and complementary expertise of the ten European partners<br />
from fi ve European countries involved, the THERADPOX<br />
project will:<br />
• generate advanced knowledge which could be translated<br />
towards a safer cancer treatment with an increased<br />
therapeutic index;<br />
• contribute to improve the quality of life of cancer patients<br />
by fewer treatments with no toxic side eff ects;<br />
• lead to the proposal of new guidelines and standards for<br />
the development of OVs;<br />
• strengthen the competitiveness of Europe in the war<br />
against cancer.<br />
TREATMENT<br />
Problem<br />
<strong>Cancer</strong> still remains the second leading cause of death in<br />
Europe and in the world. THERADPOX, by providing new<br />
treatments for three major (colorectal, pancreatic and ovarian)<br />
cancers, will contribute to addressing and pursuing central<br />
directions of the European policy against cancer.<br />
Virotherapy exploits the use of natural or engineered<br />
Oncolytic Viruses (oncolytic vectors, OVs) to selectively<br />
kill tumour cells. To date, many types of OVs have been<br />
developed and have entered clinical trials. These trials demonstrated<br />
a high safety profi le of OVs, but showed limited<br />
therapeutic eff ect when used as a monotherapy. Improved<br />
effi cacy was noted when OVs were used in combination<br />
with traditional therapies (chemotherapy or radiation). However,<br />
the effi cacy and safety of virotherapy is limited by the<br />
low effi ciency of tumour cell infection, the low level of replication<br />
in some tumour cells and the ineffi cient spreading<br />
capacity within the tumour mass.<br />
THERADPOX approach.<br />
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