Imagine two people diagnosed with the same type of lung cancer. They receive the same immunotherapy treatment. One sees their tumors shrink dramatically. The other sees no benefit at all.
For years, doctors have struggled to predict who will be that lucky responder.
New research may have found a key to this puzzle. And it’s hidden in a process happening inside every single one of your cells.
Lung adenocarcinoma is the most common form of lung cancer. Treatments have improved, but they are still a blunt instrument.
Immunotherapy is a revolutionary treatment. It helps your own immune system recognize and attack cancer cells. It doesn’t work for everyone, though.
Patients can face severe side effects. They also lose precious time on a treatment that isn’t helping. A reliable way to predict success before starting is a major unmet need.
The Surprising Shift
Doctors have looked for clues in the cancer’s genes. This new study looked somewhere else entirely.
They looked at how proteins in the cancer cell are “decorated” after they are made. This process is called acylation modification. Think of it like adding different tags or flags to a protein.
These tags change how the protein works. They can tell a cell to grow, to stop, or to hide from the immune system.
Scientists knew these tags were important. But they didn’t have a way to measure their overall pattern and connect it to treatment success.
Until now.
Researchers analyzed 12 different types of these protein tags in lung tumors. They used machine learning, a form of artificial intelligence, to find patterns.
The AI created a single score from this complex data. They call it the AM.score.
A high AM.score means the tumor has a specific pattern of protein tags. A low score means a different pattern.
This score turned out to be incredibly revealing.
The study analyzed data from over 1,720 patients. The AM.score was a powerful predictor of patient survival.
Patients with a high AM.score had worse outcomes. But crucially, their tumors also had a specific feature.
They were “immunologically hot.” This means the tumors were already surrounded by immune cells trying to fight them. These are the very patients most likely to respond when immunotherapy is added to supercharge that existing attack.
The AM.score outperformed other common markers doctors use today. It was validated across eight independent groups of patients.
But here’s the catch.
This score isn’t just a predictor. It also pointed scientists directly to a cause.
The Switch That Hides The Cancer
Deep in the data, one protein kept standing out: ZDHHC18. It’s an enzyme that adds a specific “palmitoylation” tag to other proteins.
Tumors with a high AM.score had high levels of ZDHHC18. Lab experiments then showed what it does.
ZDHHC18 acts like a master switch that turns down the immune system around the tumor. When researchers “knocked out” or disabled the ZDHHC18 gene in cancer cells, the immune response surged. The cancer’s growth was hindered.
This doesn’t mean a new treatment is available tomorrow.
The AM.score is a sophisticated tool for researchers and oncologists. It could, in the future, help guide treatment decisions by identifying patients who are ideal candidates for immunotherapy.
The real-world impact hinges on what comes next.
The Limitations Are Clear
This research is based on analyzing existing patient data and lab experiments. The score needs to be tested in prospective clinical trials, where patients are followed forward in time.
The exciting findings about targeting ZDHHC18 come from cells and animal models. Developing a drug that safely blocks ZDHHC18 in humans is a long and uncertain road.
The path is now clearer. Scientists have a promising new biomarker in the AM.score. More importantly, they have a brand-new target: the ZDHHC18 protein.
The next steps will involve developing a simple test to measure the AM.score in clinical labs. At the same time, drug developers will work on creating compounds that can inhibit ZDHHC18.
The goal is to combine these advances. One day, a test might tell a patient they have a high AM.score tumor. Their doctor could then recommend a combination of immunotherapy and a ZDHHC18-blocking drug, tailored precisely to the biology of their cancer.
That is the promise of precision medicine. This research brings us one step closer.