Gene Test May Predict Who Responds to New Mesothelioma Drug
Research & Clinical Trials
Written by Sean Marchese | Edited by Amy Edel
The mesothelioma drug RSO-021 showed promise in an early trial this month. Now the same research team has a lead on who may respond before treatment even starts.
The findings come from the same drug study from researchers at the University of Vermont and University of Leicester. It was published July 14 in Nature Communications.
Genetic Findings From the Study
- Tumors with changes in BAP1 and SETD2 genes responded significantly better to the drug in lab testing on patient tissue.
- Both genes are already frequently altered in mesothelioma.
- A separate gene, SLC7A11, appeared to help some tumor cells resist the drug.
- In the lab, combining RSO-021 with a compound that blocks SLC7A11 restored the cancer cells’ sensitivity to treatment.
None of this has been tested in patients yet. It comes from laboratory work on tumor tissue samples. If it holds up in larger studies, a simple genetic test could one day tell doctors who is most likely to benefit before treatment even begins.
How Researchers Tested Real Tumor Tissue
Rather than relying only on cells grown in a lab dish, researchers tested the drug on tissue taken directly from 22 mesothelioma patients during surgery. Small pieces of real tumor were treated with the drug and watched for signs of cell death.
The results varied widely. Some tumors died off quickly. Others barely responded at all. That split gave researchers something valuable: real tumor samples to study for what separates a responder from a non-responder.
The Genes That Predicted Response
The difference came down to genetics. Tumors with alterations in a gene called BAP1 were far more likely to respond to the drug. So were tumors with changes in a related gene, SETD2.
Both genes act as tumor suppressors, meaning they normally help keep cell growth in check. When they’re damaged or missing, cells can grow out of control. But that same damage appears to make tumor cells more vulnerable to this drug’s attack.
Both genes are already known to be knocked out in a large share of mesothelioma cases. This pattern, if it holds up, could apply to a meaningful slice of patients rather than a rare subset.
The Resistance Gene
Researchers also found a reason some tumors don’t respond. A gene called SLC7A11 was more active in tumors that resisted treatment. Cancer cells that survived long-term drug exposure in the lab had far more of it than untreated cells.
SLC7A11 helps cells import a building block they need to make their own antioxidants, giving resistant cells a backup defense system. When researchers blocked SLC7A11 in the lab using a compound called erastin, resistant mesothelioma cells became sensitive to the drug again.
That’s an early but promising clue. It suggests a future combination treatment could pair RSO-021 with a second drug that shuts down this backup defense, closing off the escape route resistant cells currently use.
How This Could Shape Future Treatment
Researchers found this genetic pattern in studies that tested RSO-021 in tumor samples and lab-grown cells. Clinical trials with patients are still needed to determine if these findings can improve mesothelioma treatment.
If future clinical trials confirm these results, doctors could use BAP1 or SETD2 results to help identify who is more likely to benefit from RSO-021. This could move mesothelioma treatment closer to a more personalized approach.
You can ask your treatment team if you’ve had genetic testing that looked for changes in genes such as BAP1 or SETD2. While RSO-021 isn’t a treatment option now, your test results could indicate which clinical trial opportunities you may qualify for and future mesothelioma treatment decisions.
