Cancer Stem Cell drug gives hope
Researchers at the University of Colorado Cancer Center have released encouraging results of a phase I clinical trial of an experimental drug OMP-54F28 (FZD8-Fc) developed by OncoMed Pharmaceuticals, selectively acting on cancer stem cells.
OMP-54F28 (FZD8-Fc) is an antagonist of the Wnt-mediated signaling pathway, the inadequate activation of which is characteristic of malignant tumors of many types, including colon, breast, liver, lung and pancreatic cancers. Moreover, it is known that this signaling mechanism plays a key role in determining the fate of cancer stem cells. That is why it is the main target in the development of drugs that affect cancer stem cells.
OMP-54F28 (FZD8-Fc), as well as the related drug vaktiktumab (OMP-18R5), also developed by OncoMed Pharmaceuticals, are the first two drugs of this class that have reached the stage of clinical trials. When conducting experiments on a variety of preclinical models, OMP-54F28 (FZD8-Fc) demonstrated effective destruction of cancer stem cells, accompanied by pronounced antitumor activity, both when used individually and in combination with chemotherapeutic drugs.
The phase I clinical trial was an open-label, dose-increasing trial involving patients with late-stage solid tumors that did not respond to standard treatment. The results were evaluated in terms of safety, immunogenicity, pharmacokinetics, biomarkers and primary signs of efficacy.
In general, the drug was well tolerated, while in several of the 26 patients the disease stabilized for more than 6 months. The most common adverse effects were impaired taste sensations, weakness, muscle spasms, decreased appetite, hair loss and nausea. The severity of these side effects ranged from mild to moderate, while all of them managed to be stopped. There was also one side effect of the 3rd degree, manifested by a significant increase in the content of phosphorus in the blood. There was also one stress fracture of the sacral vertebra of moderate severity, which occurred after six cycles of therapy in one of the patients of the group receiving the maximum dosage of the drug (20 mg / kg of body weight every three weeks).
Currently, 3 clinical trials of OMP-54F28 (FZD8-Fc) are being conducted in combination with standard therapeutic protocols for the treatment of pancreatic, ovarian and liver cancer. According to one of the leaders of the work, Dr. Antonio Jimeno, there is hope that the introduction of drugs that affect cancer stem cells into standard protocols of antitumor therapy will allow suppressing the proliferation of cells inside tumors, preventing their regeneration occurring against the background of traditional chemotherapy.
The results are presented at the 50th Annual Congress of the American Society of Clinical Oncology (ASCO), held from May 30 to June 3 in Chicago, Illinois.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
Results in Phase I trial targeting cancer stem cells.
03.06.2014