Target engagement imaging of PARP inhibitors in small-cell lung cancer Academic Article uri icon

Overview

MeSH Major

  • Lung Neoplasms
  • Molecular Targeted Therapy
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Small Cell Lung Carcinoma
  • Xenograft Model Antitumor Assays

abstract

  • Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition over time to calculate effective doses for individual drugs. Using patient-derived xenografts, we demonstrate that different therapeutics achieve similar integrated inhibition efficiencies under different dosing regimens. This imaging approach to non-invasive, quantitative assessment of dynamic intratumoral target inhibition may improve patient care through real-time monitoring of drug delivery.

publication date

  • January 12, 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5766608

Digital Object Identifier (DOI)

  • 10.1038/s41467-017-02096-w

PubMed ID

  • 29330466

Additional Document Info

start page

  • 176

volume

  • 9

number

  • 1