ctDNA Markers May Predict Prostate Cancer Drug Response
Patients with advanced prostate cancer may have new ways to monitor if a specific targeted therapy remains effective.
Updated on Oct. 23, 2026 in Cancer
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A recent study from Boston researchers identifies circulating tumor DNA (ctDNA) markers that may help predict how patients with metastatic castration-resistant prostate cancer (mCRPC) respond to the targeted therapy 177Lu-PSMA-617. These findings, presented at the ESMO Annual Congress, provide new insight into why some patients achieve exceptional responses while others develop resistance to the treatment.
Why it matters
Identifying early predictors of treatment resistance could help clinicians better manage expectations and guide personalized care decisions for patients with advanced prostate cancer. This study clarifies how genomic tumor fractions and specific pathway alterations may influence the long-term effectiveness of PSMA-targeted therapies.
This retrospective study analyzed 72 patients with mCRPC, examining 154 blood samples to evaluate genomic alterations and tumor fraction. Higher baseline ctDNA tumor fraction was significantly linked to poorer survival outcomes and resistance to 177Lu-PSMA-617, though the findings remain preliminary.
The players
Alok Tewari
An oncology researcher who led the study on prostate cancer treatment resistance.
Dana-Farber Cancer Institute
A premier Boston-based research center specializing in cancer treatment and clinical trials.
The details
Researchers used low-pass whole-genome sequencing to assess copy-number burden and tumor fraction, while targeted genomic panels evaluated specific mutations. Patients with intrinsic resistance showed baseline alterations in the 9p21 locus and the PI3K/AKT/mTOR pathway, suggesting these genetic signatures may hinder drug efficacy. By profiling nucleosome positioning and copy-number variants, the team identified how tumor-derived DNA in the blood shifts as patients progress on therapy.
Timeline
July 2022 - August 2024: Study patients were treated at the Dana-Farber Cancer Institute.
October 23-27, 2026: Results were presented at the ESMO Annual Congress in Madrid.
Health Landscape
The study builds upon the clinical development of 177Lu-PSMA-617 as a standard for advanced prostate cancer management. It marks a shift toward using liquid biopsies to refine patient selection and monitor resistance in real time.
Patients undergoing PSMA-targeted therapy should speak with their oncologist about how genomic monitoring or clinical trial enrollment might inform their care. It is helpful to understand that not all cancers respond to the same therapies, and discussing individual risk factors is essential.
The takeaway
Genomic profiling may soon become a vital tool for predicting how prostate cancer responds to specialized radioligand treatments. Patients should consult their care team about whether specialized testing or clinical trials are appropriate to help monitor their specific disease progression.
Further reading
For more on evolving research, visit Cancer.
Source note: This article includes information reported by Urotoday.
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