Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug that interrupts a key stage of cell division shows promise in patients with advanced solid tumours

09.11.2006
One of the first studies to investigate the effects of a new anti-cancer drug in patients with advanced or metastatic solid tumours has shown that it is capable of halting progression of the disease, and the study has provided the first proof of the drug’s mechanism of action.

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 [1] 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.

... more about:
»Cancer »Jonge »Solid »mg/m2 »tumours

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.”

[1]EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

Emma Mason | alfa
Further information:
http://www.eortc.org

Further reports about: Cancer Jonge Solid mg/m2 tumours

More articles from Life Sciences:

nachricht Water world
20.11.2017 | Washington University in St. Louis

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>