Researchers determine that aggressive prostate and lung cancers are driven by common mechanisms

A common process in the development of late-stage, small cell cancers of the prostate and lung has recently been discovered. The discovery of these shared molecular mechanisms could lead to the development of drugs to treat prostate and lung cancers, but other small cell cancers of almost any organ as well.

The key finding of the research is as follows: Although prostate and lung cells have very different patterns of gene expression when they’re healthy, they have almost identical patterns when they transform into small cell cancers. This new 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 which generally have extremely poor prognoses. They are also known as small cell neuroendocrine carcinomas, or SCNCs. Certain cancers can evade treatment; they do this in part by changing cell types such as changing from aggressive adenocarcinoma to small cell carcinoma.

Previously some research had hinted that small cell cancers from different organs may be driven by common mechanisms, but this recent study is the first to clearly describe the steps in the evolution.

The study’s authors and collaborators explored the potential parallels between cancer types by transplanting human prostate cells with five genes, known collectively as PARCB, into mice. When the transplanted cells grew within the mice, the cells displayed unique features of human small cell neuroendocrine carcinomas.

As part of the study the team also identified that for small cell neuroendocrine carcinomas to develop in the prostate, two tumor suppressor genes, TP53 and RB1, had to be simultaneously inactivated when PARCB was introduced. TP53 and RB1 are known for protecting normal cells from transforming into cancer cells.

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 found that the similarities between the PARCB-SCNC cancers and human small cell prostate cancers were extraordinary.

Large databases of gene expression were looked at in order to compare the patterns of gene expression in their PARCB-SCNC cells to cancers of other organs. The team found that the pattern of gene expression in PARCB-SCNC cells was extremely similar to those of both prostate and lung small cell cancers.
They then tested whether PARCB genes could alter healthy cells from human lungs into small cell lung cancers. The scientists determined that this was possible.

The team is also working on mapping which genes control the entire cascade of events that underlies the transition to small cell cancer. Studying the network of the master gene regulators may lead to a new way of combating deadly cancers.

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