Manish Kohli, Director and Physician Scientist Training Program University of Utah Health, shared on LinkedIn:
“Circulating tumor DNA (ctDNA) applications in metastatic castration-resistant prostate cancer (mCRPC) have typically examined one molecular alteration at a time.
Building on our team’s long-standing NIH-funded work which include multiple R01-UH2 awards, we are developing a multiplexed liquidbiopsy assay that detects four androgen receptor (AR) alterations at both the DNA and RNA levels in a single reaction. This approach reduces cost and conserves the limited sample material available from liquid biopsies.
This effort was led by my longtime colleague Dr. Liang Wang Moffitt Cancer Center on our jointly NIH-funded awards and offers a proof-of-principle multiplexing panel that combines complementary measures of critical AR biology central to the outcomes in this cancer.
We include determinants such as copy-number alterations (CNA) in ARenhancer and ARintron1, detection of the ART878A point mutation , and detection of AR-V7 splice variants-all taken together in a single reaction.
Together, these capture DNA and RNA-level alterations that drive AR signaling and therapeutic resistance in mCRPC.
Rather than evaluating each AR alteration in isolation, this approach offers a more integrated view of AR genomic and transcriptomic changes in liquid biopsies, with the potential to inform advanced prostate cancer outcomes.
Further analytical and clinical validation is clearly needed before clinical translation, however our access to well-annotated real-world biorepositories, high-quality pre-analytic specimens, and continued NIH support provide a strong foundation.
We continue to work eagerly towards validation of the multiplexed assay approach and for defining its role in the molecular management of men with mCRPC, an illness that remains lethal.
We remain deeply grateful to NIH for sustained support of this work!”
Title: A novel multiplex digital PCR assay for simultaneous quantification of androgen receptor amplification, mutations, and splice variants in cell-free nucleic acids from metastatic castration-resistant prostate cancer
Athors: Yijun Tian, Jodie Wong, Filip Ionescu, Jingsong Zhang, Alex Soupir, Manish Kohli, Liang Wang
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