In a recent study, researchers have discovered a new kind of small-cell lung cancer (SCLC).
The discovery paves the way for developing personalized medicine approaches to target this previously unnoticed form of the disease.
Scientists suggest that cancer is not one thing, it’s actually hundreds of distinct diseases.
SCLC is cancer without a specific treatment and often spreads early.
Chemotherapy, radiotherapy, and surgery enable only 6% of patients to survive 5 years from the time of their diagnosis. About 10%-15% of all lung cancers are SCLC.
This common refrain helps explain the frustrating experience oncologists have in testing a promising new drug only to find that it works well in some patients but fails for the majority.
Such experiences have led researchers to believe that the more they can distinguish tumor types based on meaningful biological signatures, the better chance they have of finding subsets of patients that will respond to specific drug candidates.
Fresh insight comes from an analysis of gene activity in human SCLC tumors. It reveals an unexpected activity pattern in around 20% of the samples.
In the study, the research team from Cold Spring Harbor Laboratory (CSHL) found a paucity of neuroendocrine markers in pulmonary neuroendocrine cells, a cell type thought to be the source of SCLC.
To further study this minority of cells, the team used a method they developed in 2015 that employs the gene-editing tool CRISPR to screen for specific proteins that are critical to the growth of various human cancer cell lines, including SCLC lines.
Using this “CRISPR screen,” they found that a transcription factor called POU2F3 is expressed exclusively in the minority of SCLC tumors with low levels of neuroendocrine markers.
And it turns out that this variant form of SCLC tumors is derived from a separate class of rare cells called tuft cells.
The researchers suggest that developing drugs that specifically target the function of POU2F3 may be particularly effective in the subset of patients with tumors that express high levels of this transcription factor.
In the past, the team has lumped the different forms of SCLC together because they look similar on a microscope slide.
But they now have some molecular tests that can easily discriminate these malignancies.
Their findings suggest that scientists should be designing clinical studies for them separately to find therapies that might cater to the different types of tumor.
The team is currently looking for collaborators to do preclinical tests in mice to test compounds that target POU2F3.
They also plan to use their CRISPR-based stress test to look for variant types of pancreas cancer which they hope might provide similarly specific targets for treatments.
The research team is led by Christopher Vakoc, M.D., Ph.D. He is a Cold Spring Harbor Laboratory (CSHL) Associate Professor.
Yu-Han Huang is the first author on the new paper. He is currently a postdoctoral investigator in the team.
The study is reported in the journal Genes & Development.
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Source: Genes & Development.