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Updated: Jul 9, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
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.
Abstract:
The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents. CIVO also classified patient-specific tumor resistance to the most effective agent, doxorubicin, and further enabled assessment of a preclinical autophagy inhibitor, PS-1001, to reverse doxorubicin resistance. In a CIVO-identified subset of doxorubicin-resistant tumors, PS-1001 resulted in enhanced antitumor activity, increased infiltration of macrophages, and skewed this infiltrate toward M1 polarization. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors and across a diverse immunocompetent patient population may provide a foundation from which to make informed drug development decisions. This method also represents a viable functional approach to complement current precision oncology strategies. Cancer Res; 77(11); 2869-80. ©2017 AACR.
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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