Hopes that new substance will induce cancer cell suicide

September 18, 2012, Karolinska Institutet

(Medical Xpress)—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 . Some of the patients came from the Haematology Centre at the Karolinska University Hospital in, Stockholm, where the study's 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 had been activated to varying degrees, and that this had triggered the suicide program in the . 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 confined to temporary , 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."

Explore further: Drug kills cancer cells by restoring faulty tumor suppressor

More information: Sören Lehmann, et al. 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.

Related Stories

Drug kills cancer cells by restoring faulty tumor suppressor

May 14, 2012
A new study describes a compound that selectively kills cancer cells by restoring the structure and function of one of the most commonly mutated proteins in human cancer, the "tumor suppressor" p53. The research, published ...

Three is the magic number: A chain reaction required to prevent tumor formation

January 20, 2012
Protein p53 is known for controlling the life and death of a cell and has a key role in cancer research. P53 is known to be inactive in 50 percent of cancer patients. If researchers succeed in re-establishing the presence ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.