PARP inhibitors stumble in breast cancer

@article{Guha2011PARPIS,
  title={PARP inhibitors stumble in breast cancer},
  author={Malini Guha},
  journal={Nature Biotechnology},
  year={2011},
  volume={29},
  pages={373-374}
}
  • Malini Guha
  • Published 6 May 2011
  • Medicine
  • Nature Biotechnology
373 development; what’s more, its exact mechanism of action remains “unknown,” says Alan Ashworth, chief executive of the Institute of Cancer Research in London who was involved in developing AstraZeneca’s compound and holds some patents related to it. “Is iniparib acting as a weak PARP inhibitor? I don’t know,” says Ashworth. Atul Dhir, CEO of BiPar, told Nature Biotechnology that ongoing experiments are taking place to increase understanding of iniparib’s mechanism of action in addition to… 

PARP inhibitors in cancer therapy: an update

TLDR
This review is designed to provide the readers with a brief summary and an update on PARP inhibitors in the oncology field, by covering the recent patent literature and Questel Intellectual Property Portal database search.

Concepts and Molecular Aspects in the Polypharmacology of PARP‐1 Inhibitors

TLDR
Progress made in gaining insight into the molecular basis of these multiple target‐independent and target‐dependent activities of PARP‐1 inhibitors are discussed, with an outlook on the potential impact that a better understanding of polypharmacology may have in aiding the explanation of why some drug candidates work better than others in clinical settings.

Current Status of Poly(ADP-ribose) Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer

  • D. HillerQ. Chu
  • Biology, Medicine
    International journal of breast cancer
  • 2012
TLDR
The basis behind PARP inhibitors is summarized and the current status of their development in clinical trials for the treatment of TNBC is updated.

PARP1 expression in breast cancer and effects of its inhibition in preclinical models

TLDR
It is found that nuclear PARP1 protein overexpression was associated with malignant transformation and poor prognosis in breast cancer, and olaparib (novel PARP inhibitor) had antitumour effects in different breast cancer subtypes, and its combination with trastuzumab (anti-HER2 antibody) enhanced the antitumours effects of this therapy.

The long and winding road.

TLDR
A multicenter, single-stage efficacy and safety study of the PARP inhibitor olaparib in BRCA1/2-associated pancreatic cancer and a controversial feature of this study is the trial design, which has no formal hypothesis and a statistical analysis that is only descriptive in nature.

Cross-platform pathway-based analysis identifies markers of response to the PARP inhibitor olaparib

TLDR
An algorithm to predict response using the seven-gene transcription levels was developed and applied to 1,846 invasive breast cancer samples from 8 U133A/plus 2 (Affymetrix) data sets and found that 8–21 % of patients would be predicted to be responsive to olaparib.

Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo

Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors

TLDR
The differential kinase pharmacology observed among PARP inhibitors provides a plausible explanation to their different cellular effects and offers unexplored opportunities for this drug class, but alerts also on the risk associated to transferring directly both preclinical and clinical outcomes from one PARP drug candidate to another.

Targeted therapy for brain tumours: role of PARP inhibitors.

TLDR
The implications of targeting PARP on the design of new treatment regimens are discussed and inhibition of PARP function might also induce anti-angiogenic effects which might contribute to impair tumour growth.

Potential biomarkers of Poly (ADP-ribose) polymerase inhibitors for cancer therapy

TLDR
An integrated biomarker system to predict the “appropriate users” of PAR Pi may help overcome PARPi treatment failure and reveal novel insights into clinical use of PARPi.
...

References

SHOWING 1-2 OF 2 REFERENCES

PARP inhibitors blaze a trail in difficult-to-treat cancers

TLDR
Big players have been carving out a niche in the small but thriving field of poly(ADPribose) polymerase (PARP) inhibitors, as long-awaited data roll out that validate the experimental approach.

Iniparib plus chemotherapy in metastatic triple-negative breast cancer.

TLDR
The addition of iniparib to chemotherapy improved the clinical benefit and survival of patients with metastatic triple-negative breast cancer without significantly increased toxic effects.