As cancer cells evolve in response to treatment or other environmental pressures, a patient may end up with a highly diverse population of cancer cells circulating throughout their body. In these cases, a single biopsy from the tissue where the cancer originated is not enough to fully understand the cancer’s genome or how best to target it. Liquid biopsies are thus increasingly used to study circulating tumor cells (CTCs) in the blood, with single-cell CTC sequencing emerging as the next step in unraveling the mysteries of disease progression and treatment response.

A recent case report published by former Damon Runyon Clinical Investigator Himisha Beltran, MD, demonstrates the usefulness of single-cell CTC sequencing in neuroendocrine prostate cancer (NEPC), a form of prostate cancer that can evolve from pre-existing prostate cancer in response to treatment. Current methods of diagnosing and treating NEPC, which rely on tissue biopsies, can obscure the fact that it is a cancer with a highly heterogeneous cell population. In fact, this heterogeneity is exactly why NEPC is able to function as a means of treatment resistance: under the pressure of treatment, the wide array of cancer cells undergo selection and the most resistant emerge as dominant.

By conducting single-cell genomic analysis of CTCs from one NEPC patient, Dr. Beltran’s team has not only proven how much heterogeneity can exist in a single patient, but also illuminated the genetic features of these most-resistant cancer cells. Notably, some NEPC cells showed a combined loss of the tumor suppressor genes RB1, TP53, and PTEN. Further, by comparing this patient’s CTC genome with those of additional patients, the researchers found that prognoses were poorer when more than two tumor suppressor genes were altered in a single CTC.

These findings show how CTC sequencing could drastically improve our ability to monitor and predict disease course in prostate cancer. If clinicians know what alterations to look for at the single-cell level, they can ascertain how much the cancer has evolved and how the patient is likely to respond to different therapies. As the case report says, “If [the patient’s] treatment was based only on his prostate biopsy, he may have been treated very differently.” Technologies such as liquid biopsies that capture heterogeneity are thus needed to optimize care. Given the choice between a blood sample or a slice of prostate tissue, most patients would likely agree.

Read more in Nature Precision Oncology.