The drug works by blocking aurora proteins, which play a key role in cell division and are implicated in the onset and progression of cancer. It was discovered and characterised by scientists at Nerviano Medical Sciences in Italy.
Dr Maja de Jonge, a medical oncologist at the Erasmus University Medical Centre, Rotterdam, The Netherlands, told the EORTC-NCI-AACR  Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Wednesday 8 November): “So far we have tested the drug in 36 patients in a phase I clinical trial. All the patients had advanced solid cancers that were progressing at the time they entered the trial. However, in seven of these patients the disease stabilised and has remained stable in four of the patients for seven months or more. Without the drug we would have expected to see their disease continue to progress.”
Aurora proteins belong to a family of enzymes that regulate the different steps in mitosis when the cell nucleus divides into two identical cells. The enzymes help the dividing cell to share its genetic material between the daughter cells, and they are essential for cell proliferation. Aurora proteins are over-expressed in cancer and this causes unequal distribution of the genetic material, creating abnormal cells – the hallmark of cancer. However, it is only recently that scientists have started to investigate the proteins as targets for anti-cancer therapies, and this is one of the first studies to investigate an aurora kinase inhibitor in patients.
Dr de Jonge and her colleagues tested an aurora kinase inhibitor PHA-739358. Her patients had a range of solid tumours: colorectal (9), pancreatic (3), sarcoma (5), ovarian (2), kidney (2), prostate (2), cancer of the bile ducts (2), oesophageal (3) and eight others.
They tested seven different dose levels of the drug (measured in milligrams per squared metre of body surface area (mg/m2)). Two patients could not tolerate well a dose of 400 mg/m2, and 330 mg/m2 appeared to be the recommended dose. The drug was infused into the patients’ veins over a six-hour period on days 1, 8 and 15 every four weeks.
Dr de Jonge said: “So far adverse effects have been relatively minor, consisting of a transient hypertensive episode in one patient, nausea, loss of appetite, diarrhoea, a temporary shortness of white blood cells (neutropenia), which was serious enough at 400 mg/m2 in one patient for the drug to be omitted on day eight and in another patient on day 15.
“Once the dose levels reached 190 mg/m2, tests on skin biopsies showed that the drug was inhibiting the aurora B protein – in other words it was beginning to do what we expected it to.
“The aurora B protein is responsible for phosphorylating histone H3 – a protein involved in the structure of chromatin (the strands of DNA that make up chromosomes) in cells. Inhibition of aurora B results in the inhibition of phosphorylation of histone H3, thereby blocking that step in cell division. This study shows, for the first time, that the aurora kinase inhibitor PHA-739358 inhibits phosphorylation of histone H3 in the skin of patients, and therewith provides a proof for its (or one of its) mechanisms of action.”
The researchers are continuing to recruit patients in order to define the safety of the drug and the recommended dose for subsequent studies. However, they believe the results so far are promising.
“The clinical trial has proved the concept that inhibition of the aurora protein disrupts an important stage of cell division, once the dose levels reaches 190m/m2,” said Dr de Jonge. “Patients are able to tolerate the drug and dosing schedule, and it is exciting that, at this early stage in the drug’s development, there is evidence of its ability to stabilise advanced disease.”
EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
Emma Mason | alfa
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Earth Sciences
19.07.2018 | Power and Electrical Engineering
19.07.2018 | Materials Sciences