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Updated: Jun 1, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Molecular imaging of akt enables early prediction of response to molecular targeted therapy
Mahaveer S Bhojani1, Mukesh K Nyati, Lili Zhao
1Department of Radiation Oncology, University of Michigan Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Abstract:
Development of noninvasive, real-time molecular imaging tools to assess responsiveness of a given therapy may be a critical component of the success of individualized therapy approach for patients. Toward this, we have previously developed and validated molecular sensors for Akt and caspase-3 activity, and in this report, we have explored the utility of these reporters in assessing the responsiveness of tumors to a combination of gemcitabine (Gem) and cetuximab (Cet) delivered in two opposite schedules. We found that human head and neck cancer (UMSCC1) xenografts responded significantly better in a schedule where cetuximab was administered after gemcitabine when compared with the schedule of cetuximab followed by gemcitabine. Wilcoxon two-sample tests suggested that the difference in tumor volumes in two schedules became significant on day 7 (P > .05 on day 4, and P < .05 on days 7 and 10), and the difference in activity of Akt in two schedules became significant on day 4 (P < .05 on days 4, 6, and 10). Using Akt reporter activity and cubic spline interpolation, the distinction between the two schedules could be detected 2 days before using the tumor volume, suggesting that molecular imaging of Akt may allow early prediction of therapy responsiveness. We did not observe a significant difference between the two schedules in the caspase-3 activity. In summary, this proof-of-concept study provides a basis for using molecular imaging of Akt as an early indicator of therapeutic efficacy.
Insights
Molecular imaging of Akt activity can predict tumor response to gemcitabine and cetuximab therapy earlier than traditional tumor volume measurements. This approach aids in optimizing individualized cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Imaging
- Cancer Therapy
Background:
- Individualized therapy requires real-time tools to assess treatment response.
- Molecular imaging sensors for Akt and caspase-3 activity have been previously developed.
Purpose of the Study:
- To evaluate the utility of Akt and caspase-3 molecular imaging reporters in assessing tumor responsiveness to a combination therapy.
- To compare two different administration schedules of gemcitabine and cetuximab in human head and neck cancer xenografts.
Main Methods:
- Utilized noninvasive molecular imaging sensors for Akt and caspase-3 activity.
- Administered combination therapy of gemcitabine (Gem) and cetuximab (Cet) in two distinct schedules.
- Monitored tumor volumes and molecular reporter activity over time.
- Employed Wilcoxon two-sample tests for statistical analysis.
Main Results:
- Human head and neck cancer xenografts showed significantly better response when cetuximab was administered after gemcitabine.
- Differences in tumor volume between schedules became significant on day 7.
- Differences in Akt activity became significant on day 4, preceding tumor volume changes.
- Molecular imaging of Akt activity allowed for earlier detection of therapy response (2 days prior to tumor volume).
- No significant difference in caspase-3 activity was observed between the schedules.
Conclusions:
- Molecular imaging of Akt activity can serve as an early indicator of therapeutic efficacy.
- This study provides a proof-of-concept for using Akt imaging to predict treatment response in head and neck cancer.
- Optimizing drug administration schedules is crucial for effective cancer therapy.
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