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Updated: Sep 15, 2026
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
PARP inhibitor resistance mechanisms and PARP inhibitor derived imaging probes
Tony Yu1, Benjamin H Lok1,2,3,4
1Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Introduction:
Poly(ADP-ribose) polymerase 1 (PARP1) inhibition has become a major target in anticancer therapy. While PARP inhibitors (PARPi) are approved for homologous recombination (HR) deficient cancers, therapeutic resistance is a challenge and PARPi are now being investigated in cancers lacking HR deficiencies. This creates a need to develop molecular and imaging biomarkers of PARPi response to improve patient selection and circumvent therapeutic resistance.
Areas Covered:
PubMed and clinicaltrials.gov were queried for studies on PARPi resistance and imaging. This review summarizes established and emerging resistance mechanisms to PARPi, and the current state of imaging and theragnostic probes for PARPi, including fluorescently labeled and radiolabeled probes.
Expert Opinion:
While progress has been made in understanding PARPi therapeutic resistance, clinical evidence remains lacking and relatively little is known regarding PARPi response outside of HR deficiencies. Continued research will clarify the importance of known biomarkers and resistance mechanisms in patient cohorts and the broader utility of PARPi. Progress has also been made in PARPi imaging, particularly with radiolabeled probes, and both imaging and theragnostic probes have now reached clinical validation. Reducing abdominal background signal from probe clearance will broaden their applicability, and improvements to molecular synthesis and radiation delivery will increase their utility.
Insights
Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors show promise in cancer therapy. Developing imaging biomarkers is crucial for patient selection and overcoming resistance to PARP inhibitors (PARPi).
Area of Science:
- Oncology
- Molecular Biology
- Radiochemistry
Background:
- Poly(ADP-ribose) polymerase 1 (PARP1) inhibition is a key anticancer strategy.
- PARP inhibitors (PARPi) are approved for homologous recombination (HR) deficient cancers, but resistance is a challenge.
- PARPi are being explored in cancers without HR deficiencies, necessitating biomarkers for response prediction.
Purpose of the Study:
- To review established and emerging mechanisms of PARPi resistance.
- To summarize the current status of imaging and theragnostic probes for PARPi.
- To highlight the need for improved biomarkers and imaging agents for PARPi therapy.
Main Methods:
- Literature search of PubMed and clinicaltrials.gov for studies on PARPi resistance and imaging.
- Synthesis of information on resistance mechanisms, imaging probes (fluorescent and radiolabeled), and theranostics.
- Analysis of the clinical validation and future potential of imaging and theragnostic probes.
Main Results:
- Established and emerging PARPi resistance mechanisms are summarized.
- Current imaging and theragnostic probes for PARPi, including fluorescent and radiolabeled types, are reviewed.
- Imaging and theragnostic probes have achieved clinical validation, with radiolabeled probes showing particular progress.
Conclusions:
- Understanding PARPi resistance, especially outside HR deficiencies, requires further clinical research.
- Biomarkers and resistance mechanisms need further clarification in patient cohorts.
- Improvements in imaging probe applicability and theranostic utility are needed, focusing on reducing background signal and enhancing molecular synthesis and radiation delivery.
