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 Flow of cerebrospinal fluid regulates neural stem cell division
21.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
21.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>