Scientist Develop Novel Compound That Shows Promise in Targeting “Undruggable” MYC Protein for Cancer Therapy

By Tosin Clegg

Anyone familiar with the cancer research space is no stranger to the famous MYC family of proteins. These proteins are notorious regulators of cellular processes and have long been the focus of significant interest among cancer researchers, all with a common goal: to target or regulate them. In healthy state, MYC proteins are essential for cell proliferation and various other critical biological functions. However, they often go awry, placing them at the center of the majority of human cancers.

In recent breakthrough research led by OLUWATOSIN OBISESAN, the researchers identified a novel compound with the ability to target and regulate MYC, a protein long considered “undruggable.” This discovery, published in the Journal of Medicinal Chemistry, offers new hope for developing more effective cancer therapies.

The Challenge of Targeting MYC
MYC has been a thorn in the flesh of researchers for decades. While it is well established that cancer treatment would greatly benefit from regulating this family of proteins, there are currently no direct inhibitors of these protein available for patient treatment.
“MYC is implicated in about 70% of human cancers and developing a drug that can regulate this protein will revolutionize cancer treatment as we know it. Unfortunately, MYC’s lack of a suitable binding pocket for drug molecules has hindered the development of inhibitors that regulates it via direct engagement, which explains why there are currently no MYC inhibitors in the clinic available for patient use” explains Obisesan, a leading researcher in the field.

Despite these challenges, Obisesan and collaborators have successfully identified a novel compound named MY05, that selectively targets MYC in cells and disrupts its interactions.

“It was thrilling to find that MY05 engages MYC in cancer cells and regulates its activities. Even more exciting was our discovery of the compound’s potency in reducing tumor growth in animal model” Obisesan states.

The researchers employed a robust approach, starting with computer-aided screening of chemically diverse drug-like compounds. This process led to the identification of an initial compound, which led to the synthesis of a library of seven compounds, from which MY05 emerged as the lead most promising candidate.

Implications and Future Directions
“There are over 200 types of human cancers with unique dynamics. Many research efforts have gone into finding cures for these cancers, including works from our lab, but we are still a long way from the finish line. In the United States alone, the financial burden of cancer is in billions of dollars. The narrative becomes worse when we consider the number of cancer-related deaths annually which is about 600,000 in the US.” says Obisesan.

“Cancer is a leading cause of death worldwide, and the plethora of distinct cancer types does not help matters. This is why identifying a target for MYC is such a big deal. If we can successfully regulate this one protein that drives the progression of about 70% of all these distinct cancer types, imagine the world of difference we can make in patients’ lives. That’s one treatment option that thousands of people will potentially benefit from irrespective of their cancer type. The discovery of MY05 takes us a step closer to this goal” Obisesan explains.

Obisesan’s expertise as a biological chemist in the field of cancer biology is evident in her approach to this research and her other works in identifying and modulating key pathways in oncology towards the development of novel therapeutics to advance cancer treatment.

“Research in our lab is at the intersection of chemistry and biology. We employ both organic and inorganic compounds, attacking different cancer types from different angles” says Obisesan while explaining her research work.

Obisesan has worked on multiple projects leading to peer-review publications on the use of inorganic and organic compounds as anticancer agents. One of the other strategies she employs in her multifaceted approach toward cancer drug discovery involves the study of cancer metabolism. Through a successful collaboration, Obisesan and team of dedicated researchers were able to exploit breast cancer’s dependence on oxidative phosphorylation and glycolysis to identify a synergistic approach to trigger cancer cell death. The result of this intriguing research was published in the reputable Journal of Biological Chemistry.

Speaking on her drive for advancing cancer research, Obisesan speaks on the importance of approaching cancer research with the patient in mind. “Cancer is a real issue that affects real people and researchers cannot afford to be out of touch with this reality. This is why it’s important that we communicate breakthrough findings in a timely manner. Not only does it help other scientists advance their works, but it also makes information available to the people who need it the most— the patients” says Obisesan.
To ensure her work remains accessible, Obisesan not only publishes her findings in reputable journals but also presents them at scientific symposiums and conferences. She has received two separate grants to present her research to the scientific community at Sanford Burnham Prebys where she was recognized as a “Rising Star” and Vanderbilt-Ingram Cancer Centre-two reputable NCI- designated cancer centers in the United States of America-further underscoring the relevance and significance of her research.

There is little doubt that the work of this trailblazing scientist, whose research philosophy is “think patient” will ultimately revolutionize cancer treatment.