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Therapy Resistance in Cancer: Learning from Bacteria

E. coli bacteria

Here are E. coli bacteria with green fluorescent protein-labeled chromosomes. Left: Untreated control cells, small and rod-shaped. Right: The same bacteria after being treated with antibiotics. Somehow, they managed to survive, and scientists hope learning more about why this happens can shed light on treatment-resistant prostate cancer

Why is metastatic prostate cancer so hard to kill? The short answer is that nobody knows. But scientists Kenneth Pienta, M.D., the Donald S. Coffey Professor of Urology, and Director of Research at the Brady, and Sarah Amend, Ph.D., have discovered at least one way that cancer cells manage to evade the consequences of systemic treatment: they sleep through it.

As reported previously in Discovery, Amend and Pienta discovered that cancer cells enter a “stealth mode,” called the polyaneuploid cancer cell (PACC) state. They shut down and then wake up – unharmed – when the treatment is over. “This allows them to stop dividing, so they can avoid getting hurt by hormonal and chemotherapy treatments,” says Amend. To enter the PACC state, cancer cells “access a program that is present in virtually all species – including bacteria.”

George Butler, Ph.D., a postdoctoral fellow in Amend and Pienta’s laboratory, is using bacteria to study how organisms avoid treatments like antibiotics “so that we can better understand how cancer cells use these resistance programs,” says Amend. “This has the potential to open up a whole new area of research on how to cure resistant cancer.”

In other work: Pienta and Amend, looking for new biomarkers of prostate cancer that could be measured in urine and plasma, are focusing on extracellular vesicles (EVs). “EVs are nanoparticles that are secreted into biofluids such as urine and plasma by all living cells, including cancer cells,” explains Amend. “We are investigating them not only to understand their role in cancer development, but also because they may reveal valuable clinical information and have high potential as useful biomarkers.”

EVs can be difficult to study, but “our post-doctoral fellow Chi-Ju Kim, Ph.D., developed an assay that efficiently quantifies EV uptake through threedimensional (3D) fluorescence confocal microscopy,” Amend says. “We published this protocol, including a step-by-step video, so that any scientist could use it!” This assay was described in the Journal of Visualized Experiments. 

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