Drug resistance: malaria-cancer similarity?

Drug resistance: Malaria-cancer similarity?

Researchers at the Walter Reed ArmyInstitute of Research in Washington, D.C., report experimental evidence that malaria-causing parasites may be using the same defense against antimalaria drugs as cancer cells do against certain anticancer drugs.

If both cancer cells and malaria parasitesuse the same protective device, researchers might be able to apply what they know about the cancer system to the problem of malaria drug resistance, according to the investigators.

Resistance to antimalaria drugs is agrowing problem. Nearly all malaria infections in Indochina are now caused by parasites resistant to the most effective and least dangerous antimalaria agent, chloroquine. Cases that fail to respond to chloroquine have also been reported in South America and Africa.

After a meeting on cancer drug resistancerecently at the National Institutes of Health, Samuel K. Martin of Walter Reed proposed that Plasmodium falciparum, which causes most of the 2 million to 3 million malaria deaths a year, sometimes uses a mechanism similar to that of tumor cells. If so, he theorizes, it could be thwarted in the same way resistance in cultured cancer cells can be reversed.

In the Feb. 20 SCIENCE, Martin, Ayo M.J. Oduola and Wilbur Milhous report they exposed drug-resistant P. falciparum to verapamil, one of several drugs that can prevent cancer cells from ridding themselves of chemotherapy. The verapamil made the malaria parasites sensitive to chloroquine.

Some cancer cells resist chemotherapywith the help of a cell-membrane protein that grabs and ejects toxic drugs that have gotten into the cell (SN: 1/3/87, p.12; 1/24/87, p.57). Verapamil is believed to inhibit this action. Donald Krogstad at Washington University in St. Louis is investigating whether the same protein used by cancer cells is present and functional in the parasites.

According to U.S. cancer researchers,testing of verapamil in cancer patients has begun in Japan, but there have evidently been problems with side effects. The National Cancer Institute plans to try drug-resistance-reversing agents in cancer patients soon, and one researcher involved says they will try several different reversing drugs at low doses to minimize side effects. Human trials of agents that reverse malaria drug resistance will have to wait until that system is better understood, says Milhous. In the meantime, the Walter Reed researchers are watching what happens in the cancer field, and searching for agents with fewer side effects than verapamil.

Michael M. Gottesman of the NationalCancer Institute, who with Ira Pastan and other colleagues is working on cancer drug resistance, says the malaria findings "are interesting and may turn out to be very important.' They may, he says, boost the understanding of the general drug resistance process and speed the development of new drugs for both cancer and malaria.