BRFAA - Biomedical Research Foundation Academy Of Athens
Biomedical Research Foundation Academy Of AthensAcademy Of Athens


Specific ongoing research projects:

Inspired by the constant need for better treatments, our research is focused into the development of novel anticancer molecules based on conjugates with peptide targeting moieties. We are particularly interested in cell membrane receptors which become abnormal during carcinogenesis and provide a handle for the development of targeted therapeutics. We have previously been successful in targeting the Gonadrotropin Releasing Hormone Receptor (GnRH-R), providing solutions for the treatment of prostate cancer or other cancers that express this kind of cell-membrane receptor. As an example, a novel gemcitabine based conjugate developed as part of our drug discovery program displayed significant efficacy and metabolic advantages over equimolar amounts of free Gemcitabine, in in vitro and in vivo models of disease.  The utilisation of peptide targeted moieties in drug conjugates aims to increase the drug payload to the site of action, in order to minimize off-target effects. With a group of experienced collaborators, synthetic and peptide chemists from the University of Ioannina, we have been successful with this strategy by using both cytotoxic (e.g., gemcitabine) as well as antiangiogenic small molecules.


Principle of drug targeting of cancer cells, expressing a particular receptor (in this case the GnRH-R)


We have expanded our work into other types of cancer-implicated receptors such as the epidermal growth factor receptor (EGFR) and HER2. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and is one of the leading causes of cancer deaths. Similarly, breast cancer (BrCa) is one of the most common cancers among women and a leading cause of cancer related deaths. An opportunity for targeted therapy of NSCLC or BrCa and improved therapeutic approaches presents itself through the well established association of the EGFR with these two types of cancers.  We are pursuing in parallel two avenues of experimentation towards the development of specific drugs (therapeutics) for subsets of breast and lung cancers involving EGFR amplification.  By participating in a recently funded program we aim to discover novel therapeutics for NSCLC and BrCa, by generating chemotherapeutic peptide conjugate (CPC) agents that target the EGFR (HER1 and HER2 for NSCLC and BrCa respectively). Ligands that target the EGFR will be conjugated through appropriate linkers to anticancer drugs of varying complexity and therapeutic potential with established use in NSCLC and BrCa. The CPCs are designed to be optimal in terms of in vitro effects, physicochemical properties, pharmacokinetics/biodistribution, toxicity.  The above approaches are expected to lead to several patents and generate products that are suitable for preclinical, or ideally clinical evaluation.

We are also currently experimenting with the discovery, evaluation and better formulation of molecules that target non-membrane targets, e.g. the PI3K pathway, to enhance the arsenal of antitumor agents and provide solutions in unmet medical needs, using targeted single or combinational therapies.  The PI3Ka enzyme is a key protein that is frequently mutated and affects tumor initiation and progression in various cancers representing a good candidate for the development of small molecule inhibitors. We are part of an ambitious drug-discovery consortium that is currently investigating this approach.

Finally, genetic evidence by researchers within the BRFAA on a project initiated by Professor A.Efstratiadis demonstrated that Myc ablation prevented the development of mutant Kras-induced mouse pancreatic ductal adenocarcinoma, breast and prostate cancers and also lung cancer as shown by others. We demonstrated in preclinical studies that a small molecule agent Mycro3 known to target Myc, is orally available in mice and efficacious in animal models (see relevant slide).  We are currently participating in efforts to discover novel inhibitors of this specific pathway that perhaps would be suitable candidates for a clinical trial. 

The Tamvakopoulos lab is fully equipped to support all stages of pre-clinical drug development and evaluation, including a restricted-access cell culture room, an outstanding animal facility and various standard biological methods for small molecule evaluation. Central to our research activities are Mass spectrometry based approaches using State of the Art equipment that provide us with an excellent handle on studying the biodistribution properties of our targeted drugs and the possibility of identifying mechanism based biomarkers for future clinical evaluation.