Real time ex vivo chemosensitivity assay for pancreatic adenocarcinoma
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Dae Won Kim1,*, Francisca Beato1,*, Youngchul Kim2, Alexandra F. Tassielli1, Ruifan Dai1, Jason W. Denbo1, Pamela J. Hodul1, Mokenge P. Malafa1 and Jason B. Fleming1
1 Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
2 Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA
* These authors contributed equally to this work
|Jason B. Fleming,||email:||[email protected]|
Keywords: pancreatic cancer; sensitivity assay; chemotherapy
Received: April 06, 2023 Accepted: August 19, 2023 Published: September 15, 2023
Background: Patient-derived organoids (PDOs) and xenografts (PDXs) have been extensively studied for drug-screening. However, their usage is limited due to lengthy establishment time, high engraftment failure rates and different tumor microenvironment from original tumors. To overcome the limitations, we developed real time-live tissue sensitivity assay (RT-LTSA) using fresh tumor samples.
Methods: Tissue slices from resected pancreatic cancer samples were placed in 96-well plates, and the slices were treated with chemotherapeutic agents. The correlation between the chemo-sensitivity of tissue slices and each patient’s clinical outcome was analyzed.
Results: The viability and tumor microenvironment of the tissue slices are well-preserved over 5 days. The drug sensitivity assay results are available within 5 days after tissue collection. While all 4 patients who received RT-LTSA sensitive adjuvant regimens did not develop recurrence, 7 of 8 patients who received resistant adjuvant regimens developed recurrence. We observed significantly improved disease-free survival in the patients who received RT-LTSA sensitive adjuvant regimens (median: not reached versus 10.6 months, P = 0.02) compared with the patient who received resistant regimens. A significant negative correlation between RT-LTSA value and relapse-free survival was observed (Somer’s D: −0.58; P = 0.016).
Conclusions: RT-LTSA which maintains the tumor microenvironment and architecture as found in patients may reflect clinical outcome and could be used as a personalized strategy for pancreatic adenocarcinoma. Further, studies are warranted to verify the findings.
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