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
New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego
Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
17.01.2018 | Ecology, The Environment and Conservation
17.01.2018 | Physics and Astronomy
17.01.2018 | Awards Funding