- Despite declining cancer death rates, there are still some cancers for which we do not have effective treatments.
- Researchers’ understanding of the genetic mechanisms underpinning cancer has allowed them to develop effective and increasingly precise treatments.
- Some mechanisms are more fundamental to the cell machinery than others and have been harder to target.
- A phase I safety trial has reported positive results for a new drug candidate that inhibits the notoriously difficult-to-target Myc protein, thought to play a role in most cancers.
Cancer death rates have been declining for the past 20 years, dropping by 27% between 2001 and 2020 in the United States according to the
This is due to an improvement in both the diagnostic procedures, the treatments available, and an increasingly precise approach to cancer treatment made possible by gene sequencing of tumors to see which genes have mutated and are driving cancer.
Still, despite this increasing insight, many people do still die from cancer. Some carry a higher death risk than others, with lung, pancreatic and colorectal cancer causing 40% of all cancer deaths in the U.S. alone.
Due to researchers’ increasing understanding of the genome, specialists have been able to identify many drug targets for cancers caused by specific mutations.
Often, these mutations are on genes that code for proteins that control the cell cycle, driving increased cell division, meaning that faster or unregulated growth can occur in a tissue leading to the development of a tumor.
One protein that is particularly important for cell division in many different tissues of the body is known as Myc, and its expression is regulated by the Myc gene.
The importance of this protein became clear in the 90s due to extensive research on it. One of the researchers who studied it was Prof. Gerard Evans, now at Cambridge University in the United Kingdom. He
In an interview with Medical News Today he explained:
“Myc is what’s called a
transcription factor. That is, it activates expression or regulates [the] expression of target genes. And it’s a very, what we call pleiotropicone, which means it has many, many downstream functions. It’s known to regulate at least maybe half or a third of all genes in the human genome. But it’s very contextual, what it regulates — it doesn’t do the same thing every time in every tissue.”
He, as well as other teams of scientists, went on to show that the Myc protein was present in many different cancers, and often cancerous mutations interfered with the activity of Myc, driving cell proliferation.
Prof. Evans said: “So Myc is a sort of gateway, that is, a very short-lived protein. It’s only expressed when there are signals telling the cell that’s expressing it that there’s damage and it needs to replicate. As soon as those signals disappear, Myc disappears because it’s very short-lived.”
“So it is exactly like a foot on the gas pedal of a car,” he explained. “What then seems to happen is that even if Myc is not mutated in some cancers, some of these genes that regulate cell division are mutated and they’re locked in the on position. In cancers, it looks like Myc is behaving as it normally does. But it’s just being relentlessly activated by mutations elsewhere in the cell.”
As Myc is implicated in so many cancers, including pancreatic, lung, and colorectal cancers, it provides an obvious target for cancer drugs. Designing one has not been easy, as the Myc protein is a complex shape, acts differently in different tissues, and is involved in many important processes.
Despite these challenges, researchers have recently found that a protein able to reach the cell nucleus can inhibit Myc in cancers.
The mini-protein known as OMO-103 is based on
Researchers at Peptomyc and Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain worked together to develop OMO-103.
Researchers from VHIO presented data demonstrating the safety of OMO-103 in phase I clinical trials at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona on October 28, 2022.
The trial included 22 patients with advanced solid tumor cancers including pancreatic, bowel, and non-small cell lung cancers who had previously been treated with different regimes.
The participants received different doses of OMO-103 once a week by infusion. CT scans completed at week 3 showed the cancers had stopped growing in eight of them.
Of these patients, two had pancreatic cancer, three had colon cancer, one had non-small lung cancer, one had a form of sarcoma, and one had salivary gland cancer. One patient with pancreatic cancer showed tumor shrinkage of 8% after 6 months.
The treatment showed only mild side effects, which were mainly due to the infusion of the protein. Participants reported chills, fever, nausea, rashes, and hypotension (low blood pressure). These reactions were more severe with the higher doses, but all were easily treatable with medication.
The next step is to see how OMO-103 performs in combination with other cancer drugs, said Dr. Soucek in an interview with MNT:
“Now that we have shown that Omomyc is so safe in the phase I and it also has clear signs of activity, we want to expand its use to more patients, of course. And the next step would be to test it in combination with standard of care, any new drug needs to be eventually approved and used that in combination with current therapies, no new drug is used on its own anymore.”
She said she thought it would have particular relevance for patients with pancreatic and non-small cell lung cancers, though it could potentially be useful for the many cancers affecting Myc activity.
The drug was unusual, as it did not target the mutation present in cancer, but rather the mechanism the cancer mutations drove, she said.
Prof. Evans commented: “It takes a lot of courage to try these completely new modalities of drugs. And so you know, [for] a lot of people including myself […] it was going to be real tough to make this Myc inhibitor work. But the Peptomyc people seem to have really got it looking like it’s effective and they can deliver it. So I would say one of the most underestimated virtues of good science is courage.”