In a recent study, UCLA researchers have discovered a common process in the development of late-stage, small cell cancers in the prostate and lung.
These shared molecular mechanisms may lead to the development of drugs to treat not just prostate and lung cancers, but small cell cancers of almost any organ.
Small cell cancers of the lung, prostate, bladder, and other tissues were long thought to be similar in name alone — and they were treated by oncologists as different entities.
Prostate and lung cells have very different patterns of gene expression when they’re healthy, but almost identical patterns when they transform into small cell cancers.
The research suggests that different types of small cell tumors evolve similarly, even when they come from different organs.
Cancers that become resistant to treatment often develop into small cell cancers — also known as small cell neuroendocrine carcinomas, or SCNCs — which generally have extremely poor prognoses.
Certain cancers can evade treatment in part by changing cell types — from aggressive adenocarcinoma to small cell carcinoma, for example.
Previous research hinted that small cell cancers from different organs may be driven by common mechanisms.
This UCLA study is the first to so clearly describe the steps in their evolution.
The team explored the potential parallels between the cancer types by transplanting human prostate cells with five genes, known collectively as PARCB, into mice.
When those cells grew in the mice, they displayed unique features of human small cell neuroendocrine carcinomas.
The team also identified that for small cell neuroendocrine carcinomas to develop in the prostate, two tumor suppressor genes, TP53 and RB1, which are known for protecting normal cells from transforming into cancer cells, had to be simultaneously inactivated when PARCB was introduced.
Additional tests confirmed striking similarities between the PARCB-SCNC cells and small cell prostate cancer cells from humans. In particular, RNA expression and the turning on and off of certain genes were nearly identical.
The team suggests that the similarities between the PARCB-SCNC cancers and human small cell prostate cancer samples were extraordinary.
If you blindly gave the data sets to any statistician, they would think they were the same cells.
The team also looked at large databases of gene expression, to compare the patterns of gene expression in their PARCB-SCNC cells to cancers in other organs.
They found that the pattern of gene expression in PARCB-SCNC cells was extremely similar to those of both prostate and lung small cell cancers.
Next, they tested whether PARCB genes could alter healthy cells from human lungs into small cell lung cancers, and the scientists found that they could.
The team now is working on mapping which genes control the entire cascade of events that underlies the transition to small cell cancer.
The study was led by Dr. Owen Witte, founding director of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and professor of microbiology, immunology and molecular genetics.
Dr. Jung Wook Park is the study’s first author.
The findings are published in the journal Science.
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