The "grey cardinal" of cancer has been attacked
The proto-oncogenic protein Myc is one of the most desirable and inaccessible targets in oncology because it plays a key role in the occurrence and maintenance of many common tumors in humans, including breast, prostate, lung and ovarian cancers. To date, no drug that inhibits the expression of the mutated MYC gene has been approved for clinical use.
Spanish researchers have developed the OMO-103 peptide, which can penetrate cells and reach the nucleus. Earlier, during in vitro and mouse experiments, they showed that OMO-103 successfully suppresses the ability of MYC to stimulate tumor growth, blocking its function of controlling the flow of information from common mutations found in cancer.
The Phase 1 clinical trial began in April 2021, Dr. Elena Garralda and her colleagues from the Val d'ebrona Institute of Oncology in Barcelona included 22 volunteers in it to evaluate the safety of OMO-103 and find out if there are any early signs that it prevents tumor growth. The patients had solid tumors of various localization, including pancreatic cancer, intestinal cancer and non-small cell lung cancer. All of them had previously received intensive treatment (from 3 to 13 different courses).
OMO-103 was administered intravenously once a week in six different doses – from 0.48 to 9.72 mg per kg of weight. The researchers performed a tumor biopsy at the beginning of the study and after three weeks of treatment to assess the activity levels of the MYC gene and other biological indicators of cancer.
By October 10, 2022, eight out of 12 patients who underwent a CT scan after nine weeks had stable disease, and treatment stopped the growth of cancer. Of these, two had pancreatic cancer, three had colon cancer, one had non–small cell lung cancer, one had sarcoma and another had salivary gland cancer.
It is noteworthy that one patient with pancreatic cancer remained in the study for more than six months, his tumor decreased by 8%, and the amount of circulating cancer DNA decreased. A patient with a tumor of the salivary gland showed stabilization of the disease and is still in the study after 15 months.
The most common side effects associated with treatment were mild reactions – chills, fever, nausea, rash and low blood pressure. Higher doses were associated with more reactions, but all of them were easily treatable. One patient had acute pancreatitis, and this was the only dose-limiting reaction.
Analysis of the absorption and excretion of OMO-103 showed that it remained in the blood serum for at least 50 hours. But researchers have previously experimentally proved that the concentration of the drug in the tumor is at least four times higher than in the blood. In addition, even after long-term treatment, there were no antibodies to the drug, which can reduce its amount and, therefore, make it less effective.
Preliminary results of the study were presented at the 34th EORTC-NCI-AACR (European Organization for Research and Treatment of Cancer) Symposium, which is taking place these days in Barcelona, Spain.
OMO-103 is the first MYC inhibitor to successfully pass Phase 1 clinical trials. The recommended dose for phase 2 is 6.48 mg/kg.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to EurekAlert!: Results revealed from phase I clinical trial of the first drug to successfully inhibit the MYC gene, which drives many common cancers.