Identifying Characteristics of ‘Zombie’ Cancer Cells May Help Predict Relapse

Dormant cancer cells have been shown to revive themselves back into an active state — and researchers have solved the science behind these so-called “zombie cells” that are likely to relapse after surgery.

In a study published in the journal, Cell Genomics, a team from Rutgers University in New Jersey revealed that the same types of proteins — AP1 transcription factors — drive both entry to and revival from senescence, an arrested state that cells at risk for malignant transformation can enter into after carcinogenic stress such as the expression of cancer-causing oncogenes.

For patients, the discovery of this information may lead to advances in treatment.

“One of the things that we found (and) that we validated across, I think, 1,000 different colorectal cancers, is that if we are able to get (patients’) genomic information from their tumor, we identify two signatures that predict whether the tumor will relapse after surgery, or whether it will not,” explained lead author Ricardo Iván Martínez-Zamudio, assistant professor of pharmacology at Robert Wood Johnson Medical School and research member of Rutgers Cancer Institute of New Jersey.

That information, Martínez-Zamudio explained, could potentially guide post-surgical treatment for patients with the disease.

“They can already foresee that it's going to come back (or not),” he said.

In the long term, Martínez-Zamudio, said these findings could eventually lead to preventative measures.

“We're trying to validate it more, to a degree that we can say, ‘OK, so now it's worth it to invest a little bit of time and research into developing molecules that prevents this factor from working,’” he said. “Well, that, as you can imagine, I can take a few more years to validate that, but that is what we're working on right now.”

Rutgers researchers, who studied senescence in colorectal cancer cells, believe the revival process is similar in other tumor types, the university stated in a news release. The team from the Herbig laboratory at Rutgers University Medical School examined the progression of cultured cells, then confirmed their findings in tissues taken from patients.

Cells that overexpress the cancer-causing oncogenes enter oncogene-induced senescence (OIS) following a period of hyperproliferation, the Rutgers study explained.

“Cells with features of OIS have been detected in early neoplastic and premalignant lesions in humans, some of which remain inactive for years,” the authors wrote. Some of those lesions can subsequently lose their senescence features and progress to advanced stages of cancer.

“The evolution of premalignant lesions into more aggressive cancer stages raises the possibility that senescent cells within these lesions develop mechanisms to escape from OIS,” the authors wrote. “Elucidating these mechanisms can open inroads into the early detection of, patient stratification for, and intervention into premalignant lesions that remain susceptible to cancer progression.”

Researchers found that the protein POU2F2 was critical in “promoting escape from senescence,” according to the news release, which stated that its overexpression and increased activity are associated with cell inflammation and proliferation, as well as decreased patient survival.

POU2F2, the news release stated, has been implicated in the progression of various cancers and might be a viable drug target.

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