Researchers find drug combo that slows treatment-resistant prostate cancer
New CapabilitiesMichigan team reverses the cell identity switch that lets prostate tumors evade treatment
Today: JCI Insight publishes two-drug combination studyNew here? Follow stories to track developments over time. Create a free account to get updates when stories you care about change.
Overview
Updated 1 hour agoSome prostate cancer tumors survive treatment by changing what they are—losing glandular identity and adopting stem-cell-like traits, a process called transdifferentiation. A University of Michigan team showed in JCI Insight that combining two drug classes reverses many of those changes and sharply slows tumor growth in mice.
Treatment-resistant prostate cancer has few options once tumors stop responding to hormone therapy. The combination approach targets the identity switch itself, and the team plans to develop clinical trials to test it in patients.
Why it matters
Treatment-resistant prostate cancer has few options today. This drug combo targets the resistance mechanism itself, potentially adding years for patients who run out of choices.
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The academic medical center at the University of Michigan, home to the Rogel Cancer Center and the Alumkal laboratory.
A peer-reviewed journal published by the American Society for Clinical Investigation, focused on translational and clinical research.
Timeline
June 2026 September 2026
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JCI Insight publishes two-drug combination study
Today PublicationUniversity of Michigan researchers show BET bromodomain and DNMT inhibitors together reverse transdifferentiation and slow tumor growth in mice.
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PIM1-targeting drug shows promise in resistant prostate cancer
Research findingA separate research team reports that degrading PIM1 with a PROTAC molecule increases oxidative stress in prostate cancer cells and improves cell death.
Historical Context
3 moments from history that rhyme with this story — and how they unfolded.
CDK4/6 inhibitors for hormone-resistant breast cancer (2015-2017)
Palbociclib, ribociclib, and abemaciclib were approved after trials showed that adding a CDK4/6 inhibitor to hormone therapy extended progression-free survival in advanced breast cancer patients whose tumors had developed resistance.
Combination therapy became the standard of care for metastatic HR-positive, HER2-negative breast cancer.
Demonstrated that blocking the specific pathways resistance mechanisms rely on can meaningfully extend survival.
Shows the path from preclinical discovery to clinical standard of care when a second drug targets the resistance mechanism directly.
Osimertinib for EGFR T790M-resistant lung cancer (2015)
After first-generation EGFR inhibitors stopped working because of a new resistance mutation (T790M), osimertinib was developed to target that specific resistance mechanism. Trials showed dramatic response rates in patients who had progressed on earlier drugs.
Osimertinib became standard second-line therapy, then moved to first-line treatment.
Established that understanding a specific resistance mechanism allows the development of drugs that hit it directly.
Like the Michigan approach, it turns knowledge of the resistance mechanism into a targeted treatment strategy, rather than just managing symptoms of progression.
Neuroendocrine transformation of prostate cancer (clinical phenomenon)
Under prolonged androgen deprivation, a subset of prostate adenocarcinomas transform into small cell neuroendocrine carcinomas—an aggressive form with a fundamentally different cellular identity. This is the clinical manifestation of lineage plasticity, the same phenomenon the new study targets.
Patients who transform typically progress rapidly on hormone therapy and have poor survival.
Established the concept that prostate cancer cells can change identity under treatment pressure, transforming how researchers think about resistance.
The transdifferentiation in the new study is the same biological phenomenon, now addressed mechanistically with drugs rather than just observed.
