For the first time, researchers inhibited a cancer-causing gene's function to cure cancer

The research team presented their findings at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
Mert Erdemir
Cancer malignant cells.
Cancer malignant cells.

iStock / koto_feja. 

For the first time ever, researchers developed a drug that specifically targets the key cancer-causing gene "MYC" and inhibits its activity safely and effectively, according to a press release.

The research team presented their findings at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.

"MYC is one of the 'most wanted' targets in cancer because it plays a key role in driving and maintaining many common human cancers, such as breast, prostate, lung, and ovarian cancer. To date, no drug that inhibits MYC has been approved for clinical use," said Dr. Elena Garralda, Director of the Early Drug Development Unit at Vall d'Hebron Institute of Oncology (VHIO) in Barcelona and a member of the scientific committee for the meeting.

A mini protein called OMO-13

The VHIO scientists devised a mini-protein named "OMO-103," which can get inside cells and reach the nucleus, and tested it on mice. The results have shown that it can block MYC's ability to boost tumor growth by hindering its function of controlling the flow of information from many common genetic mutations found in cancer.

The researchers started a phase I clinical trial in April 2021 to evaluate the safety of OMO-103. The trial included 22 patients who had different tumor types, such as pancreatic, bowel, and non-small cell lung cancers and had previously undergone other treatments.

A total of six dose levels of OMO-103, ranging from 0.48 to 9.72 mg per kg of patient weight, were administered intravenously, once each week. In order to measure the levels of MYC gene activity and other biological indicators for cancer, the researchers obtained biopsies from the tumors at the beginning of the trial and three weeks following the treatment.

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After nine weeks, eight out of twelve patients who underwent CT scans showed stable illness, meaning that the treatment had halted cancer growth. Two of them were diagnosed with pancreatic cancer, three had colon cancer, one had non-small lung cancer, one had a sarcoma, and one had salivary gland cancer.

"It's still very early days to assess activity of the drug, but we are seeing stabilization of disease in some patients. Remarkably, one patient with pancreatic cancer stayed on the study for over six months, his tumor shrank by eight percent, and there was a reduction in tumor-derived DNA circulating in the bloodstream. The patient with a salivary gland tumor has stable disease and is still in the study after 15 months," said Dr. Garralda.

"The most exciting thing is that biological markers show that we are targeting MYC successfully. In addition, the adverse side effects are mostly mild, which is important when we start to think about next steps and combining OMO-103 with chemotherapy or other therapies."

Showing mild adverse effects

The subjects showed some mild adverse side effects such as chills, fever, nausea, rash, and low blood pressure. One patient, however, had pancreas inflammation, which was the only dose-limiting reaction seen during the trial.

According to the analysis of how OMO-103 was absorbed and processed in the body, it stayed in blood serum for at least 50 hours.

"We have experimental evidence that this could be a significant underestimate of how long the drug remains in the tumor. Evidence from our work in mice suggest drug concentrations in the tumor that are at least four-fold higher than in the blood," said Dr. Garralda. "In addition, even after long-term treatment, we could not detect any anti-drug antibodies, which can decrease the amount of drug available and therefore make it less effective."

"OMO-103 is the first MYC inhibitor to successfully complete a phase I clinical trial and to be ready to proceed to a phase II trial. We have determined the recommended dose for phase II to be 6.48mg/kg," she concluded.

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