Robotic Platform Uncovers Hidden Vulnerabilities in ‘Persister’ Cancer Cells

A new robotic system developed at UC San Francisco is enabling researchers to study the rare cancer cells that survive initial treatment—and revealing shared weaknesses that could lead to more effective therapies.

The Challenge of Persister Cells

Persister cells are a deadly minority. As few as 1 in 1,000 tumor cells, they survive initial drug treatment and can later seed new tumors. Yet they are genetically identical to the bulk tumor, making them extraordinarily difficult to identify and study.

Adding to the challenge, their survival traits are often temporary, which has historically made persister cells a moving target for researchers.

A Robotic Breakthrough

Researchers at UC San Francisco have now developed a robotic platform that can handle thousands of miniature tumors at once. The system works with 384-well plates, using a robotic arm to apply precise drug doses via sound waves, then imaging the surviving cells.

The team tested 94 drug candidates on persister cells from two types of lung cancer—requiring 10,000 individual experiments. The scale of this approach allowed them to identify patterns that would have been invisible with conventional methods.

Surprising Findings

The results defied expectations. Nine drugs consistently weakened persister cells across different tumor samples, indicating shared vulnerabilities.

"A few years ago, people were still asking whether persister cells were real. Now we can find them and test ideas for how to eliminate them." — Xiaoxiao "Vany" Sun, PhD, first author

"We expected each tumor to behave as its own special case. Instead, we found patterns that held up across many different samples, suggesting there may be underlying rules that can help predict which therapies are most likely to work." — Steve Altschuler, PhD, co-senior author

Future Directions

The team plans to expand the platform to more tumor types and treatment conditions, with the goal of creating a comprehensive dataset. This resource could help researchers eliminate persister cells before drug-resistant disease develops.

The findings were published in Science Advances on June 12.