Biomedical Research Foundation Academy Of AthensAcademy Of Athens
Research Highlights :Study in the Design of Novel Targeted Molecules for the Treatment of Solid Tumors

A new paper was recently published online in Cancer Research from the Tamvakopoulos Group and colleagues at BRFAA, the University of Ioannina and the NCSR “Demokritos”. 

The Tamvakopoulos laboratory’s main objective is to design and evaluate novel targeted molecules for the treatment of solid tumors such as prostate, breast, lung and pancreatic cancer.

What’s the main idea of the recent study?
These new targeted molecules are active solely at the tumor site, with limited side effects in comparison to traditional anticancer drugs, and are on the way to one day becoming successful anticancer drugs.  This approach is consistent with the Biomedical community’s aspiration to provide patients with more efficacious, less toxic drugs, as well as “personalized medicine”.

How can this be accomplished?
By exploiting cancer cell-specific characteristics:  Some proteins (called receptors) on the surface of tumor cells are either mutated or are present in high numbers in the tumors of specific patient populations.  New chemical and biological technologies are applied to target these receptors for selective anti-cancer treatment.

What has been done in the past?
The concept of generating cancer therapeutics that target specific cell-surface receptors has been a driving force of drug development over the past few years.  Besides our team, there have been other groups that have mainly utilized cytotoxic drugs (e.g., doxorubicin, docetaxel) by linkage to targeting peptides in order to provide patient-specific treatments with very promising results at the preclinical or clinical level.

What is unique about this paper?
Unlike healthy cells, the cancer cells that make up tumors need oxygen and nutrients to live, and therefore grow blood vessels in a process called angiogenesis. A better understanding of the prostate cancer microenvironment and the central role of angiogenetic kinases in tumor growth led us to investigate an alternative to the traditional cytotoxic drug strategy, by combining sunitinib, a small antiangiogenic approved drug with the targeting peptide [D-Lys6]-GnRH. With the help of our collaborators, we rationally designed several analogs of sunitinib and experimented with the targeting of prostate and breast cancer cells, expressing one particular cancer related receptor called gonadotropin-releasing hormone receptor. Our results showed that our targeted molecule (called SAN1GSC) was superior in terms of efficacy compared to the non-targeted version. Importantly, animals treated with SAN1GSC had minimal off-target toxicity based on blood and cardiac function measurements.

Our results offer preclinical proof of concept for SAN1GSC as a novel molecule that selectively reaches the tumor site and blocks angiogenesis with negligible hematotoxicity and cardiotoxicity, thus encouraging its further clinical development and evaluation.


Constantin Tamvakopoulos is an Investigator (Associate Professor Level) at the Biomedical Research Foundation and his laboratory’s main focus is to explore and develop novel therapeutic approaches with a particular focus on cancer.

Orestis Argyros is the first author of the publication. He is a Postdoctoral fellow in the Tamvakopoulos Lab and his work involves developing novel anti-cancer and anti-angiogenic therapeutics.

Theodoros Karampelas is a Postdoctoral fellow in the Tamvakopoulos Lab at the Biomedical Research Foundation and his work involves developing novel anti-cancer conjugated therapeutics.

Full Citation:
Peptide-drug conjugate GnRH-sunitinib targets angiogenesis selectively at the site of action to inhibit tumor growth.
Orestis Argyros, Theodoros Karampelas, Xenophon Asvos, Aimilia Varela, Nisar Sayyad, Athanasios Papakyriakou, Constantinos H Davos, Andreas G Tzakos, Demosthenes Fokas, and Constantin Tamvakopoulos.
Cancer Res. 2015 Dec 8. pii: canres.2138.2015.