In 2023, a Veteran sat in his doctor’s office after exhausting every available treatment for advanced prostate cancer. He had tried seven different therapies. Each worked for a while, but the cancer kept coming back, spreading even to his brain.
At that point, there were no options left.
That’s when his doctor, Maneesh Jain, MD, tried something different: he looked for a protein called HER2, something usually linked to breast cancer, and not widely known to be expressed in prostate cancer.
After just four treatments with a newer, targeted medication, the patient’s tumors shrank by more than half, and he started to feel better again (1).
What is HER2?
HER2 is a protein that can act like a gas pedal for cancer, helping it grow and spread.
It’s well known in breast cancer, where testing for HER2 is routine and helps guide treatment. But in prostate cancer, HER2 hasn’t traditionally been part of standard testing. This is because in the past, finding HER2 did not matter for prostate cancer treatment. The treatments that worked for HER2-expressing breast cancers did nothing to shrink prostate tumors.
Why This Matters
HER2 may be more common in prostate cancer than previously thought, especially in more aggressive cases of prostate cancer (2). Now there are newer options called antibody-drug conjugates that can target even low levels of HER2 — levels that might have been ignored in the past.
One of these drugs, trastuzumab deruxtecan, is designed to:
- Find cancer cells that have HER2
- Attach to them
- Deliver chemotherapy directly into targeted cells and nearby cells
This kind of treatment is sometimes called a “smart” therapy because it targets cancer more precisely. It has already helped people with certain types of breast cancer, including those with low HER2 levels. Trastuzumab deruxtecan is the drug that Jain used for his patient who had run out of options. Now, Jain is exploring whether it could help other prostate cancer patients, too.
What’s Happening Next?
Jain is working with other researchers across multiple institutions to study this approach more carefully in a clinical trial. The goal is to understand how effective trastuzumab deruxtecan is for patients with metastatic prostate cancer that is linked to HER2.
This is still early research. Not every patient will benefit, and these treatments are not yet standard for prostate cancer. However, Jain’s success with two patients certainly makes it a worthwhile path to explore (3).
References
- Lap CJ, et al. Response of human epidermal growth factor receptor 2–expressing prostate cancer to trastuzumab deruxtecan. Ann Intern Med. 2024. doi:10.7326/ANNALS-24-01409
- Estephan F, et al. The prevalence and clinical significance of HER2 expression in prostate adenocarcinoma. Ann Diagn Pathol. 2023;XX:152219. doi:10.1016/j.anndiagpath.2023.152219
- Rajendran R. Clinical response to novel combination of trastuzumab deruxtecan and abiraterone in HER2-expressing metastatic castration-resistant prostate cancer. Oncologist. 2025;30(9):oyaf207. doi:10.1093/oncolo/oyaf207
About the Investigator
Maneesh Jain, MD, is an Associate Professor of Medicine at the GW School of Medicine and Health Sciences and a practicing hematologist/oncologist at the VA Medical Center in Washington, DC. He can be reached via Maneesh [dot] Jain [at] va [dot] gov (email).
