Dr Grieb on MYC in CRC

Brian C. Grieb, MD, PhD, instructor, clinical medicine, clinical fellow, Division of Hematology/ Oncology, Department of Medicine, Vanderbilt University Medical Center, discusses historical barriers to targeting the MYC oncogene in patients with colorectal cancer (CRC) and the rationale for an ongoing phase 1/2 clinical trial that may demonstrate an effective way to target MYC in CRC and other solid tumors. 

Dr Grieb on the Future of Targeting MYC in CRC

MYC is an oncogenic transcription factor that regulates gene expression, Grieb says. Although most other transcription factors regulate a few select genes that they can turn on manyfold, MYC controls many genes and turns them on 2- or 3-fold, Grieb notes.MYC also programs cells for proliferation that, when uncontrolled, can induce tumor formation and cancer survival, Grieb explains.

Although MYC was the second oncogene ever discovered, effective small molecule inhibitors of MYC have yet to be developed, Grieb emphasizes. Current research is focused on understanding the necessary proteins for MYC to function as a transcription factor and learn how those proteins interact with MYC to determine whether they can be used in a therapeutic setting, Grieb says.

Dr Grieb on Omomyc in CRC

The protein Omomyc (OMO-103) represents a potential avenue for inhibiting MYC, Grieb explains. Omomyc research has moved from the lab to the ongoing, open-label, 2-part, phase 1/2 MYCure trial (NCT04808362), which is investigating the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of the protein in patients with advanced solid tumors, including non–small cell lung cancer, triple-negative breast cancer, and CRC. The dose-escalation part of this trial evaluated Omomyc at 5 dose levels to determine the recommended phase 2 dose (RP2D). The dose-expansion part treated patients at the RP2D to further evaluate the safety and antitumor activity of this protein.

Although the findings from this trial are not yet available, they will be important for understanding the efficacy of Omomyc and the mechanism of action of this protein, Grieb concludes.