Nelfinavir shows promise as a cancer therapy

Some HIV protease inhibitors appear to have activity against certain cancers, according to US laboratory research published in the September 1^st edition of Clinical Cancer Research. The investigators, from the US National Cancer Institute (NCI), found that nelfinavir (Viracept, ritonavir (Norvir) and saquinavir (Invirase) all had cancer-inhibiting properties. The results for nelfinavir were most promising, and a clinical trial involving humans has been designed to test the safety and efficacy of the drug as a cancer remedy.

Ironically, nelfinavir recently had its European licence suspended and was subjected to a near-global recall after it was found that an error during manufacture had lead to contamination with excess amount of a potentially cancer-causing agent.

Protease inhibitors are known to inhibit the activation of a protein called Akt that is implicated in the development of many types of cancer including non-small cell lung cancer.

The NCI investigators therefore conducted animal and test tube studies to determine the efficacy of six protease inhibitors against non-small cell lung cancer and 60 human cancer cell type cultures obtained from human tissues affected by nine different malignancies.

Doses of the protease inhibitors known to be safe and effective as HIV therapy were used in the study. Nelfinavir, ritonavir and saquinavir inhibited the growth of non-small cell lung cancer and every cell type in the set of 60 kinds of cancer cell.

Particularly encouraging results were for nelfinavir and saquinavir, with both drugs equally likely to inhibit further tumour growth and to induce natural cell death. The investigators speculated that the molecular structure of these drugs, which is not present in the other compounds they tested, may be responsible for the effectiveness of these two drugs.

Nelfinavir yielded the most promising results of all, producing two kinds of cell death – apoptosis and non-apoptotic death. Nelfinavir was also found to have the greatest Akt inhibition. The drug was also found to have activity against breast cancer cells that that developed resistance to existing breast cancer drugs, such as tamoxifen, and cancerous cells that were resistant to radiation therapy.

Researchers are now investigating the safety and efficacy of nelfinavir as a cancer therapy in a phase-one clinical trials in humans. “Our data suggest that, given its wide spectrum of activity and ability to be administered through two different transmission routes [oral and intraperitoneal], nelfinavir could be successfully repositioned as a cancer therapeutic”, commented Dr Philip Dennis of the NCI.