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Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas
| Content Provider | Scilit |
|---|---|
| Author | Yang, Sherry X. Kummar, Shivaani Steinberg, Seth M. Murgo, Anthony J. Gutierrez, Martin Rubinstein, Larry Nguyen, Dat Kaur, Gurmeet Chen, Alice P. Giranda, Vincent L. Tomaszewski, Joseph E. Doroshow, James H. |
| Copyright Year | 2009 |
| Description | Targeting the poly (ADP-ribose) polymerase (PARP) pathway for cancer treatment has been an active area of pre-clinical and clinical research. We aimed to determine whether the PARP inhibitor ABT-888 hits its therapeutic target in tumors by immunohistochemistry during a Phase 0 trial conducted at the National Cancer Institute. The expression of poly (ADP-ribose) (PAR) and full size PARP-1 were quantitatively examined by immunohistochemistry in paraffin-embedded tumor biopsies at baseline and 3-24 h after a single oral dose (25 or 50 mg) of ABT-888. Baseline PAR levels were moderate to high in three patients with non-Hodgkin lymphomas, and one each with small cell lung cancer, squamous cell carcinoma of the tongue and melanoma; low in two patients with cutaneous T-cell lymphoma and one with adenocarcinoma of external ear canal. A significant decrease in PAR (median decrease 30.2, range -13.1 to -69.8) was achieved after drug administration (n = 6 pairs; p = 0.03), whereas an increase in PARP-1 expression was observed in five of the six tumors. This resulted in a decrease in the ratio of PAR to PARP-1 in tumor biopsies (median -6.76, range -0.41 to -22.59; p = 0.03). ABT-888 hits its therapeutic target by significantly reducing PAR levels and the ratio of PAR to PARP-1 in human tumor cells detected by immunohistochemistry. Baseline tumor PAR levels vary considerably among patients who entered this phase 0 study. This underscores a need to investigate baseline PAR levels in association with response in future preclinical and clinical studies. |
| Related Links | https://www.landesbioscience.com/journals/cbt/06YangCBT8-21.pdf |
| Ending Page | 2009 |
| Page Count | 6 |
| Starting Page | 2004 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.8.21.9917 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 21 |
| Volume Number | 8 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2009-11-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Pathology Treatment Tumor Immunohistochemistry Adp Parp Abt Ribose Poly Par Levels |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
