Machine-learning aided in situ drug sensitivity screening predicts treatment outcomes in ovarian PDX tumors

Max J. Cotler, Khalil B. Ramadi, Xiaonan Hou, Elena Christodoulopoulos, Sebastian Ahn, Ashvin Bashyam, Huiming Ding, Melissa Larson, Ann L. Oberg, Charles Whittaker, Oliver Jonas, Scott H. Kaufmann, S. John Weroha, Michael J. Cima

    Research output: Contribution to journalArticlepeer-review


    Long-term treatment outcomes for patients with high grade ovarian cancers have not changed despite innovations in therapies. There is no recommended assay for predicting patient response to second-line therapy, thus clinicians must make treatment decisions based on each individual patient. Patient-derived xenograft (PDX) tumors have been shown to predict drug sensitivity in ovarian cancer patients, but the time frame for intraperitoneal (IP) tumor generation, expansion, and drug screening is beyond that for tumor recurrence and platinum resistance to occur, thus results do not have clinical utility. We describe a drug sensitivity screening assay using a drug delivery microdevice implanted for 24 h in subcutaneous (SQ) ovarian PDX tumors to predict treatment outcomes in matched IP PDX tumors in a clinically relevant time frame. The SQ tumor response to local microdose drug exposure was found to be predictive of the growth of matched IP tumors after multi-week systemic therapy using significantly fewer animals (10 SQ vs 206 IP). Multiplexed immunofluorescence image analysis of phenotypic tumor response combined with a machine learning classifier could predict IP treatment outcomes against three second-line cytotoxic therapies with an average AUC of 0.91.

    Original languageEnglish (US)
    Article number101427
    JournalTranslational Oncology
    StatePublished - Jul 2022


    • Drug delivery
    • Ovarian cancer
    • Patient derived xenograft
    • Personalized medicine

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research


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