Chemotherapy drugs kill malaria parasite
15 March 2011
The Ecole Polytechnique Federale de Lausanne's Global Health
Institute (GHI) and the Institut National de la Santé et de la Recherche
Médicale (Inserm) in France have discovered that a class of chemotherapy
drugs originally designed to inhibit key signaling pathways in cancer
cells also kills the parasite that causes malaria.
The discovery could quickly open up a whole new strategy for
combating this deadly disease.
The research, published online in the journal Cellular
Microbiology, shows that the malaria parasite depends upon a
signaling pathway present in the host — initially in liver cells,
and then in red blood cells — in order to proliferate. The enzymes
active in the signaling pathway are not encoded by the parasite, but
rather hijacked by the parasite to serve its own purposes.
These same pathways are targeted by a new class of molecules
developed for cancer chemotherapy known as kinase inhibitors. When
the GHI/Inserm team treated red blood cells infected with malaria
with the chemotherapy drug, the parasite was stopped in its tracks.
Professor Christian Doerig and his colleagues tested red blood
cells infected with Plasmodium falciparum parasites and showed that
the specific PAK-MEK signaling pathway was more highly activated in
infected cells than in uninfected cells.
When they disabled the pathway pharmacologically, the parasite
was unable to proliferate and died. Applied in vitro, the
chemotherapy drug also killed a rodent version of malaria (P.
berghei), in both liver cells and red blood cells. This
indicates that hijacking the host cell’s signaling pathway is a
generalized strategy used by malaria, and thus disabling that
pathway would likely be an effective strategy in combating the many
strains of the parasite known to infect humans.
Malaria infects 250 million and kills 1-3 million people every
year worldwide. Efforts to find a treatment have been marred by the
propensity of the parasite to quickly develop drug resistance
Once in the body, it hides from the immune system inside liver
and blood cells, where it proliferates. The discovery that the
parasite hijacks a signaling pathway in the host cell opens up a
whole new strategy for fighting the disease.
Instead of targeting the parasite itself, the host cell
environment could be made useless to it, thus putting an end to the
deadly cycle. Because this strategy uniquely targets host cell
enzymes, the parasite will be deprived of a major modus operandi for
development of drug resistance — selection of mutations in the drug
Several kinase-inhibiting chemotherapy drugs are already used
clinically, and many more have passed stage 1 and stage 2 clinical
trials. Even though these drugs have toxic effects, they are still
being used or considered for use over extended periods for cancer
Using them to combat malaria would involve a much shorter
treatment period, making the problem of toxicity less acute. The
authors of the study suggest evaluating these drugs for antimalarial
properties, thus drastically reducing the time and cost required to
put this new malaria-fighting strategy into practice.
1. Audrey Sicard et al. Activation of a PAK-MEK
signalling pathway in malaria parasite-infected erythrocytes.