Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer.

Expert Opinion on Investigational Drugs
Giulio EvangelistiSimone Ferrero

Abstract

Introduction Patients with high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and current chemotherapy regimens for treating advanced disease are far from satisfactory. Prexasertib (LY2606368) is a novel checkpoint kinase inhibitor (CHK) under investigation for the treatment of HGSOC. Data from a recent phase II trial showed promising efficacy and safety results for treating wild-type BRCA HGSOC. Areas covered This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to ...Continue Reading

References

Jan 1, 1982·Cancer Chemotherapy and Pharmacology·A H CalvertK R Harrap
Jun 17, 2000·Investigational New Drugs·A MonksE A Sausville
Sep 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·S MatsuokaS J Elledge
Nov 27, 2001·Science·D CortezS J Elledge
Jun 5, 2003·Cancer Cell·Jiri Bartek, Jiri Lukas
Jun 7, 2003·Science·Lee Zou, Stephen J Elledge
Feb 12, 2004·The Journal of Biological Chemistry·D Alwyn DartNicholas D Lakin
Jul 29, 2004·DNA Repair·Oscar Fernandez-CapetilloAndré Nussenzweig
Apr 4, 2006·Molecular and Cellular Biology·Eva PetermannKeith W Caldecott
Jun 3, 2006·Journal of Cellular Physiology·Luciana E Giono, James J Manfredi
Aug 30, 2008·Molecular Cancer Therapeutics·Alessandra BlasinaKenna Anderes
Nov 20, 2008·Gynecologic Oncology·Siriwan TangjitgamolPisake Lumbiganon
Jun 2, 2009·DNA Repair·Dana Branzei, Marco Foiani
Jan 6, 2010·EMBO Molecular Medicine·Ana M Mendes-PereiraAlan Ashworth
Feb 24, 2010·Nature Reviews. Molecular Cell Biology·Mary Ellen Moynahan, Maria Jasin
Mar 3, 2010·PLoS Genetics·Jon H Chung, Fred Bunz
Jun 29, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N ColomboUNKNOWN ESMO Guidelines Working Group
Nov 3, 2010·Advances in Cancer Research·Joanne SmithDavid A Gillespie
May 6, 2011·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Michael FriedlanderUNKNOWN Gynecologic Cancer InterGroup
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Aug 5, 2011·Drugs·R Wendel Naumann, Robert L Coleman
Aug 13, 2011·The Cochrane Database of Systematic Reviews·Ahmed ElattarRaj Naik
Feb 22, 2012·Frontiers in Pharmacology·Brian GabrielliSandra Pavey
Feb 5, 2013·Expert Opinion on Biological Therapy·Umberto Leone Roberti MaggioreSimone Ferrero
Mar 20, 2013·Cellular and Molecular Life Sciences : CMLS·Mallikarjun PatilZheng Dong
Jul 3, 2013·Expert Opinion on Investigational Drugs·Matteo MorottiSimone Ferrero
Sep 10, 2013·Cell Cycle·Khanh DoShivaani Kummar
Sep 28, 2013·Expert Opinion on Investigational Drugs·Umberto Leone Roberti MaggioreSimone Ferrero
Apr 29, 2014·Lancet·Gordon C JaysonJonathan A Ledermann
Oct 25, 2014·Therapeutic Advances in Medical Oncology·Daniela LuveroJonathan A Ledermann
Nov 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bella KaufmanSusan M Domchek
Nov 19, 2014·Journal of Molecular Cell Biology·Laura ZanniniGiacomo Buscemi

❮ Previous
Next ❯

Citations

Jun 3, 2021·Biomolecules·Igor A SchepetkinMark T Quinn

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.