Scientists from the University of Southern California (USC) have openednew drug for the treatment of ovarian cancer, which is able not only to reduce the dosage of medications taken by oncological patients, but also to be effective even against the background of resistance to drugs.
A new drug, tested so far only in the laboratory on tumor cells of patients with ovarian cancer, and in mice, was introduced to the medical community last month in the official journal of the National Academy of Sciences of the United States (PNAS).
"We are striving to create a new generation of drugs to overcome the resistance of cancer cells to drug exposure said Shili Xu, a USC graduate student and one of the authors of PNAS.
This drug is a member of a new class of cytotoxic agents known under the acronym PACMA, which were first discovered as a result of pharmacological screening of the order of 1, 00 different chemical connections. The effect of each of these compounds was tested on cancer cells in the laboratory of Nuri Niamati, professor of pharmacology and pharmaceutical sciences at the University of Southern California and one of the authors PNAS. In the future, cooperation in scientific research was conducted with Nikos Petasis, who is also one of the authors of the journal of the National Academy of Sciences of the United States, and, in addition, professor of chemistry of the South California university. Together, scientists investigated the chemical substances that represent the class of PACMA compounds, which was quickly reported in the journal "Medical Chemistry" last year.
In the process of researching and optimizing the antitumor properties of PACMA compounds, Alexey Butkevich, a graduate student at the Petasis laboratory, synthesized more than 80 new substances. One of them, called PACMA31, showed the best results for ovarian cancer cells, and was selected from the total number of compounds as a potential drug.
In a PNAS publication, Xu and colleagues presented PACMA31 as a potent selective inhibitor of the disulfide isomerase protein, which is highly expressed in ovarian cancer. PACMA31 is taken orally and accumulates only in malignant cells, which reduces the likelihood of side effects in the normal tissues of the body. In addition, PACMA31 - the so-called "irreversible" drug. Linking with protein disulfidizomerazoy, he does not lag behind him until the properties of the protein is not violated. Such irreversibility of PACMA31 causes its longer action, which, in turn, reduces the dosage of the drug.
"We are exploring how our new drug works in combination with first-line drugs in the treatment of ovarian cancer Niamati says. Currently, the first-line drugs for the treatment of ovarian cancer are paclitaxel, which prevents the cancer cell from dividing by inhibiting the process reorganization of the microtubule network, and carboplatin, which facilitates the cross-linking of adjacent pairs of guanine bases in the DNA of a cancer cell, leading to death cells. PACMA31 fights cancer in a somewhat different way, acting on disulphidisomerase, thus interrupting the folding process (packing) of the protein, during which the proteins assume a unique spatial structure that allows them to function correctly.
Due to a fundamentally different mechanism of action, PACMA31 may be useful to patients who are not exposed to paclitaxel or cisplatin. "When patients have no other choice, in the long term we will be able to offer them a new medicine says Niamati. He also stressed that, despite the need for further research on PACMA31, even now it can be said that this drug is non-toxic and effective. The scientist believes that the potential of this drug is not limited to treating only ovarian cancer.
According to Petasis, the discovery of a new drug with a previously unknown mechanism of action - an outstanding example of interdisciplinary interaction between chemists, biologists, pharmacologists and other biomedical researchers.