Gábor Mező
Gábor Mező
Research Advisor
Doctor of Science (DSc)
Contact details
Address
1117 Budapest, Pázmány Péter sétány 1/a.
Room
441
Phone/Extension
1433
Links
  • 1. Natural sciences
    • 1.4 Chemical sciences
      • Organic chemistry
Development of peptid-drug conjugates for targeted tumor therapy

Classical chemotherapy used to the cancer treatment has a number of side effects, which significantly impair the patient's quality of life during treatment. To avoid side effects, so-called targeted tumor therapy may be suitable. In this case, the chemotherapeutic agent is attached to a targeting moietyl, such as a peptide, which recognizes specific or overexpressed receptors on tumor cells and selectively delivers the drug to tumor cells. Thus,  health  tissues remain intact that may reduce the unwanted side effects.  The selection of homing peptides can be based on literary knowledge or with the help of phage display libraries. However, the structure of the selected peptides can be further modified to produce better-acting and/or more enzyme-resistant conjugates, which can also increas their bioavailability. The linker system also plays an important role, because it must ensure the stability of the conjugate in the bloodstream and the release of the free active drug or its active metabolite in the tumor cell.  Due to the large number of tumor types, experimentation with numerous conjugates is important for effective personalized therapy. Therefore, our research focuses on producing conjugates with sufficient efficiency for as many tumor types as possible, which could be potential tumor therapeutic agents in the future.

Formulation of antitumor agents to increase their bioavailability

Several active substances with very high cytotoxic effects cannot be used in tumor therapy due to their high toxicity. In order to reduce unwanted toxicity but maintain their antitumor effect, several solutions are being experimented with. One such possibility is to enclose the active substance in a liposome or other nanoparticle, from which the active substance is released only in tumor cells. The selectivity of the formulated active substance can be further enhanced by attaching targeting peptides to the appropriate nanoparticle, which recognize specific or over-expressed receptors appearing on the surface of tumor cells that results in selectiv internalization of the attached construction into tumor cells. In addition to a patent-pending design, with which we carry out further preclinical studies, we aim to produce and test second-generation products. Within this framework, we prepare new active drug molecules, other types of nanocarriers and their targeted variants in order to develop effective, potential drug candidate for tumor therapy.

Extending targeted tumor therapeutic approaches to resistant cancer models

Cancer is the second cause of death worldwide. In spite of the improvement of diagnostic tools and therapeutic approaches, cancer is still a leading medical problem to be solved. In many cases, it is believed that the patient is completely cured but unfortunately in time cancer relapse. One of the main reasons of cancer renewal is based on resistant cancer cells including cancer stem cells (CSCs). These special subpopulations of cancer cells are highly resistant to drugs from different reasons, therefore their elimination from the body is almost impossible. They can survive under treatment and can form new cancer colonies with time at distant parts of the body. In contrast with sensitive tumor cells, CSCs express limited type of receptors on their surface, therefore, the very promising targeted tumor therapy has limited effect on such type of resistant tumor cells. This therapeutic approach is based on targeting moieties (e.g. peptides) that specifically recognize the receptors on tumor cells and can selectively deliver the attached drug to tumor cells. Consequently, the unwanted side effects of anticancer drugs can be reduced. In our present research we would like to find appropriate receptors on resistant cancer cells including CSCs that can be attacked with drug delivery systems to eliminate not only sensitive but also resistant cancer cells to prevent cancer relapse. For this purpose, new drug constructs will be developed, their structure will be optimized to reach the highest efficacy, and the best drug candidates will be studied in vivo on tumor bearing mice.