Graphics to Understand the p53 and MDM2 Cancer Pathway

medical cover art cancer patients by SayoStudio for AACR
Editorial cancer art for AACR, by SayoStudio, one of many science graphics we create for cancer research.

Our broad mission at SayoStudio is to share scientists’ discoveries in engaging, informative visual ways. But, we also have a vested interest in science that directly impacts our daily lives.

Like many of you, many of us at SayoStudio have close family members who have battled cancer. It gives us pride, and so much hope to create science graphics that help explain exciting cancer research: from figures for scientists like Ben Izar at the University of Columbia, to editorial art for non-profits like AACR, to animations for life science companies turning their research into life-saving drugs.

We recently finished an animation (top of page) for Rain Oncology, a cancer therapeutics development company. You can peek at our animation process in our biotech animation case study. In this post, we’re looking at the illustrated diagram to explore some of the scientific details of the cancer target, protein MDM2.

Understanding and Sketching the MDM2 Cancer Pathway

The initial concept sketch shows the delicate balance between p53 (blue) and MDM2 (red), and how Milademetam (green) may be able to restore that balance. On the left is a healthy cell, center—an unhealthy cell, and right—a Milademetan treated cell. Sketch ©SayoStudio
A previous illustration of MDM2’s involvement in cancer. On the left, MDM2 (red) is overactive, and cancer ensues. On the right, Milademetan inactivates MDM2, allowing p53 (blue) to activate pathways to halt cancer.

As with all of our projects, we got started learning about the MDM2 pathway so that we could effectively communicate the story. To understand MDM2, we have to step back and learn about the protein p53. The protein p53, often called the guardian of the genome, is critical to halting a cancerous cell’s growth before it turns into a tumor.

It’s implicated in 50% of all cancers. But how? In normal cells, p53 activates the DNA repair pathway when DNA is damaged, or even proactively destroys cells that can’t be saved. Unfortunately, it’s also been incredibly difficult to design a drug to target it, for numerous reasons (sorry, that’s another story for another day!).

Thus, scientists have been searching for other targets in the complex pathway. Enter the protein MDM2. MDM2 is an inhibitor of p53. Think of MDM2 as handcuffs on our hero, p53. So even if p53 is active, out-of-control MDM2 hinders p53 from kick-starting fixes to the mutated DNA that may lead to cancer.

Restoring the balance of P53 and MDM, Cancer Therapy Graphic

The finished science diagram uses a combination of 3D art and graphic symbols to emphasize the changing balance of MDM2 and p53—shown in a healthy cell, a cancer cell, and a Milademetan-treated cell—in one master image. © SayoStudio.

At the heart of the story, is a balance of power between p53 and MDM2. By tweaking this balance, Rain scientists have determined that MDM2 is a viable target. They’ve identified a small molecule that deactivates MDM2, allowing p53 to resume its job. It’s this small molecule, named Milademetan, that is showing promising results in clinical trials.

Once MDM2 is deactivated by Milademetan, p53 can regain its function guarding against mutated DNA and out-of-control cell growth. You can learn more about Rain Oncology’s clinical trials, currently targeting difficult-to-treat cancers like liposarcoma.

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