Tuesday, August 17, 2021

Repeat Cancer Offenders

Good news! Cancer is history!

"Most cancer-related deaths occur not from the first tumor to arise in a patient but from cancers that reappear months or years after treatment.
Scientists think that a group of rare cancer cells, called persister cells, might contribute to such recurrence. Persister cells account for only a fraction of cancer cells; as their name suggests, they persist despite drug treatment, can survive in the body long enough to gain new mutations that enable them to evade drugs, and ultimately, drive recurrent tumor growth. ...
Although scientists knew cycling persister cells existed, their relative rarity among persisters—roughly 5 in 1,000 persister cells retain the ability to “cycle” or divide—has made them difficult to isolate and characterize. ...
To their surprise, the researchers also found that cycling persister cells relied on metabolism based on fatty acids, rather than glucose—typically, cancer cells are known to thrive on sugar. These observations were consistent across multiple cancer cell lines, in a mouse model of cancer and in samples from human lung tumors."

"Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell’s clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. ... The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence."

Repeat Offenders | Harvard Medical School Analysis shows how a rare population of cancer cells contributes to disease relapse

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