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This Week in Science: Apr 15, 2016

In Science this week, a University of Melbourne-led team reports data showing parasites that develop resistance to the antimalarial agent atovaquone are unable to pass that resistance to their offspring. Since mutations in the gene cytochrome b (cytB) are known to promote drug resistance, the investigators focused on three atovaquone-resistant strains of a malarial parasite that infects rodents, each with a different cytB mutation. They found that two of the gene mutations resulted in developmental defects in the parasite zygotes, while the third mutation resulted in complete infertility in the parasites. Cross breeding parasites with and without the mutations revealed that the mutations are not passed to offspring, while transmission attempts involving 750 mosquito bites resulted in a single atovaquone resistance transmission that was not able to be transmitted further. The team concluded that the cytB mutations impair the lifecycle of the parasites when they are living in mosquito hosts and therefore cannot be passed on. Similar mutations in the human malaria parasite Plasmodium falciparum were also found to impair the ability of parasites to infect mosquitos.

And in Science Translational Medicine, a multi-institute research group presents a study identifying alterations to the JAK2 gene in chemotherapy-resistant patients with triple-negative breast cancer (TNBC), pointing to the possibility of targeted therapy for these patients. By sequencing tumor samples, the researchers found that JAK2 was more frequently amplified in chemotherapy-treated TNBC patients than untreated patients, and that treated patients were more likely to have aggressive and resistant tumors — pointing to a role for JAK2 in drug resistance. They further discovered that a general JAK inhibitor could not stop the growth of JAK2-amplified breast cancer cells, even in combination with chemotherapy. However, the use of a JAK2-specific inhibitor significantly reduced TNBC tumor growth in mice when used in combination with chemotherapy.