Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Hopes that new substance will induce cancer cell suicide

The p53 gene plays a key role in the prevention of cancer, by blocking cell growth and triggering programmed cell death or apoptosis.

If, however, p53 has mutated and become defective, the cancer cells can acquire the ability to evade apoptosis and become more resistant to therapy. Researchers at Karolinska Institutet and Karolinska University Hospital have now obtained results from the first tests using a new substance that can restore the function of defective p53 and activate apoptosis in cancer cells.

The substance is known as APR-246 and has now been tested on humans in a phase I/II study, which was conducted on 22 patients with advanced blood or prostate cancer. Some of the patients came from the Haematology Centre at the Karolinska University Hospital in, Stockholm, where the studys lead investigator, consultant Dr Sören Lehmann is based. The remainder of the patients were from other clinics in Gothenburg, Lund, Uppsala and Örebro.

The patients received daily infusions of APR-246 for four days. When the researchers analyzed the cancer cells taken before and after treatment, they saw indications that the p53 gene had been activated to varying degrees, and that this had triggered the suicide program in the cancer cells. Ten patients could be evaluated as regards the development of their cancer, and in two of them there were signs of tumour regression.

However, the study was actually not designed to test the clinical effects but to ascertain how well the substance was tolerated by the body. With the main adverse reactions confined to temporary tiredness, nausea, headache and confusion, their results would suggest that the substance is well tolerated.

"The side-effects were totally different to those produced by conventional chemotherapy, which bodes well for designing combination therapies," says Dr Lehmann. "And it's in precisely this kind of combination that we think the substance has the greatest potential. In previous laboratory studies we've seen that APR-246 has generated synergy gains when used with chemotherapy due to the mutually enhancing effects of both substances."

Defective p53 is considered one of the most common factors behind the development of cancer. In some cancers, such as ovarian cancer, the vast majority of tumours have defective p53. In total, the p53 tumour suppressor gene is mutated in at least half of all tumours.

"In theory, a drug that restores p53 function should be effective against many different kinds of cancer, provided that the individual tumour contains defective p53," says study team member Professor Klas Wiman. "We should keep in mind, however, that tumours are very complex."

APR-246 was discovered by Klas Wiman and colleagues at Karolinska Institutet, and the present study was led from Karolinska University Hospital in association with Aprea AB. Aprea AB's principal shareholder is Karolinska Development, a company listed on the NASDAQ OMX Stockholm exchange. Professor Wiman is co-founder and shareholder of Aprea, and a member of its board.


Sören Lehmann, Vladimir J.N. Bykov, Dina Ali, Ove Andrén, Honar Cherif, Ulf Tidefelt, Bertil Uggla, Jeffrey Yachnin, Gunnar Juliusson, Ali Moshfegh, Christer Paul, Klas G. Wiman and Per-Ola Andersson

Targeting p53 in vivo: A first-in-man study with the p53-targeting compound APR-246 (PRIMA-1MET) in refractory hematological malignancies and prostate cancer

Journal of Clinical Oncology, early online publication 10 September 2012, doi: 10.1200/JCO.2011.40.7783.
Link to the abstract in PubMed
Journal website
For further information, please contact:
MD, PhD, Principal Investigator Sören Lehmann
Work: +46 (0)8-585 826 77 Mobile: +46 (0)70-760 48 82

Press Office | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>