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 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.
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.
The new 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.
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.
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.
“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.”
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