PARP inhibitors: A new era of targeted therapy

Tangutoori, Shifalika; Baldwin, Paige; Sridhar, Srinivas

doi:10.1016/j.maturitas.2015.01.015

Cited by 132 publications

(107 citation statements)

References 31 publications

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“…From a clinical point of view, PARP1 has garnered significant interest for cancer treatment over the past decade. Several inhibitors are now in phase 1 and 2 clinical trials as chemotherapy sensitizing agents, and the inhibitor olaparib was recently approved by the US food and drug administration and European commission for the treatment of advanced ovarian cancer (56). Along with the established role of PARP1 in neurodegeneration, the findings presented here argue that these selective inhibitors, with their well-defined pharmacodynamics, blood brain barrier permeability, and tolerability, may also be excellent candidate therapeutics for the treatment of neurological injury.…”

Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration

Brochier

Jones

Willis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Therapeutic options for the restoration of neurological functions after acute axonal injury are severely limited. In addition to limiting neuronal loss, effective treatments face the challenge of restoring axonal growth within an injury environment where inhibitory molecules from damaged myelin and activated astrocytes act as molecular and physical barriers. Overcoming these barriers to permit axon growth is critical for the development of any repair strategy in the central nervous system. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a previously unidentified and critical mediator of multiple growth-inhibitory signals. We show that exposure of neurons to growth-limiting molecules-such as myelin-derived Nogo and myelin-associated glycoprotein-or reactive astrocyte-produced chondroitin sulfate proteoglycans activates PARP1, resulting in the accumulation of poly(ADP-ribose) in the cell body and axon and limited axonal growth. Accordingly, we find that pharmacological inhibition or genetic loss of PARP1 markedly facilitates axon regeneration over nonpermissive substrates. Together, our findings provide critical insights into the molecular mechanisms of axon growth inhibition and identify PARP1 as an effective target to promote axon regeneration.poly(ADP-ribose) polymerase | PARP1 | PAR | axon | regeneration

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Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration

Brochier

Jones

Willis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…A recent clinical trial using ABT-888 (Veliparib), an oral PARP inhibitor targeting TMPRSS2-ERG fusions has recently been carried out (see clinicaltrials.gov, identifier: NCT01085422, NCT01576172). Numerous studies show that PARP inhibitors, when added to hormone therapy, contribute to tumor regression especially those expressing TMPRSS2-ERG and clinical trials with several PARP inhibitors are currently being conducted in various cancers to assess their toxicities, efficacies and benefit as monotherapies or combined with radiation or other chemotherapeutic agents [166,167].…”

Section: Gene Fusionsmentioning

confidence: 99%

The hallmarks of castration-resistant prostate cancers

Katsogiannou

Ziouziou

Karaki

et al. 2015

Cancer Treatment Reviews

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“…This treatment can be applied as monotherapy or in combination with radiation or other chemotherapeutic agents. Clinical trials testing poly ADP ribose polymerase (PARP) inhibitors are currently under development phase (123)(124)(125).…”

Section: Poly Adp-ribose Polymerase (Parp) Inhibitorsmentioning

confidence: 99%

Pancreatic cancer from bench to bedside: molecular pathways and treatment options

Kosmidis¹,

Sapalidis²,

Kotidis³

et al. 2016

Ann. Transl. Med.

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In the last forty years the pancreatic cancer treatment has made advances, however; still novel drugs are needed. It is known that the five year survival rate remains around 5%. The best treatment option still remains surgery, if patients are diagnosed early. In the last decade the biology of pancreatic cancer has been vastly explored and novel agents such as; tyrosine kinase agents, or vaccines have been added as a treatment perspective. The big challenge is now to translate this knowledge in better outcomes for patients. In this current review we will present information from pancreatic cancer diagnosis to molecular pathways and treatment options; current and future.

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PARP inhibitors: A new era of targeted therapy

Cited by 132 publications

References 31 publications

Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration

Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration

The hallmarks of castration-resistant prostate cancers

Pancreatic cancer from bench to bedside: molecular pathways and treatment options

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