Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and

Jason P Frazier1, Jessica A Bertout1, William S Kerwin1

  • 1Presage Biosciences, Inc., Seattle, Washington.

Cancer Research
|April 2, 2017
PubMed

Insights

Novel Comparative In Vivo Oncology (CIVO) technology precisely models patient-specific cancer drug responses. This approach aids in developing more effective cancer therapies by overcoming tumor heterogeneity and predicting clinical efficacy.

Area of Science:

  • Oncology
  • Translational Medicine
  • Drug Development

Background:

  • Precision medicine faces challenges in cancer drug development due to tumor heterogeneity and patient diversity.
  • Current preclinical models often fail to accurately predict clinical drug efficacy.

Purpose of the Study:

  • To develop and validate a novel technology for testing patient-specific tumor responsiveness to multiple drugs simultaneously in vivo.
  • To assess the potential of a preclinical autophagy inhibitor to overcome drug resistance.

Main Methods:

  • Comparative In Vivo Oncology (CIVO) arrayed microinjection technology was used to test drug responses directly in patient tumors.
  • The study involved 18 canine patients with soft tissue sarcoma (STS).
  • CIVO assessed responses of cancer cells and immune infiltrates to chemotherapy agents and an autophagy inhibitor (PS-1001).

Main Results:

  • CIVO successfully captured complex, patient-specific tumor responses to various chemotherapy agents.
  • The technology identified patient-specific resistance to doxorubicin.
  • In doxorubicin-resistant tumors, PS-1001 demonstrated enhanced antitumor activity and modulated the immune infiltrate towards M1 polarization.

Conclusions:

  • CIVO technology provides a viable functional approach to complement precision oncology strategies.
  • Simultaneous evaluation of multiple drugs and combinations in living tumors can inform drug development decisions.
  • This method offers a foundation for improving predictions of clinical drug efficacy in diverse patient populations.

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