MOSCOW, March 22. /TASS/. A team of Russian scientists from four research centers - Moscow Institute of Physics and Technology (MIPT), Moscow State University, National University of Science and Technology (MISIS), and the Skolkovo Institute of Science and Technology (Skoltech) - provided an overview of molecules capable of assisting in the fight against prostate cancer and in the diagnosis of this illness, reports MIPT press service.
«Researchers have identified 11 compounds of great promise. All these substances are currently tested in clinical trials and demonstrated the necessary qualities at the stage of preclinical studies», - says press-release.
Prostate cancer is one of the most common cancers in men. Today, the majority of anti-cancer therapies are not selective enough and may have a detrimental effect not only on cancer cells, but on the healthy cells of the body as well. That is why it is so important to develop such drugs that would attack the cancer cells exclusively, which will increase the effectiveness of treatment and reduce the negative impact of therapy on the body as a whole. However, to ensure the drug selectivity, the scientists need some object which is present only in cancer cells - and not anywhere else: a cancer marker.
The well-known marker for prostate cancer is PSA (prostate specific antigen), which is already used in medicine for the diagnosis of prostate cancer. However, for a number of reasons, PSA is considered as an insufficiently precise target. A promising alternative for the diagnosis and treatment of prostate cancer is PSMA (prostate specific membrane antigen). In the case of cancer, prostate tissues contain almost 10 times as many of these markers as healthy tissues of the prostate gland. Also, diagnosis by means of this marker can detect the tiniest metastases (secondary distant tumors).
"PSMA is one of the most promising biological targets for the development of new hybrids of selective PSMA ligands with antitumor medicinal substances or molecular diagnostic tools for their targeted delivery to the site of the disease - particularly in the case of prostate cancer," says Yan Ivanenkov, head of the MIPT Laboratory of Medical Chemistry and Bioinformatics and a lecturer in MIPT.
Biocatalyst and target
All molecules capable of binding to PSMA can be divided into three groups: antibodies, aptamers, and ligands. Antibodies are proteins synthesized by the immune system. Aptamers are peptide molecules or fragments of DNA/RNA, capable of selectively binding to specific target molecules. Ligands are substances of a rather arbitrary nature which interact with the biocatalyst.
Comparing all three groups, the researchers concluded that ligands are the most promising group. Ligands, in our case, are molecules the size and weight of which are most suitable for synthesizing. Besides, they also have good pharmacokinetic parameters.
Scientists have been searching for the ligands compatible with PSMA since the 1990s and phosphorus compounds were among the first ligands of PSMA, which showed high efficacy on cancer cells. However, their pharmacokinetic parameters were insufficient for the conduct of clinical trials.
Later, compounds with -SH groups have become alternatives to phosphorus-containing chemicals. They demonstrated high bioavailability when taking medication by mouth (oral administration), and also they better penetrated the cell membrane. However, these drugs had insufficient selectivity and metabolic stability. That is, they adversely affected not only cancer cells and, besides, they mutated in the course of biochemical reactions in the body.
New class of ligands needed to be free of the deficiencies of their predecessors. The next candidates for treating prostate cancer were the compounds formed on the basis of urea. Currently, this is the most widely studied type of PSMA ligands.
The article was published in the Journal of Drug Targeting.