A new kind of small-cell lung cancer (SCLC) has recently been discovered by the researchers which will show the path for developing personalized medicine approaches to target the disease which remained previously unnoticed. The study was published in the journal Genes & Development.
Cancer is the compilation of hundreds of different diseases. Oncologists face a crucial problem that new anti-cancer drugs are effective to only a handful of the patients while for the majority it becomes a failure. Such experiences have led the researchers to believe that there should be more and more categorization of tumors which will improve the chances of patients to respond to specific drugs.
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 small-cell lung cancer One type of cancer in desperate need of new drug is SCLC, cancer without a specific treatment that often spreads early.
Christopher Vakoc and his associates did an analysis of gene activity in human SCLC tumors and found a paucity of neuroendocrine markers in pulmonary neuroendocrine cells, a cell type thought to be the source of SCLC.
To have a greater insight of these minority of cells, Vakoc and colleagues used a method 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,” the team found that a transcription factor called POU2F3 is expressed exclusively in the minority of SCLC tumors with low levels of neuroendocrine markers. It turns out that this variant form of SCLC tumors is derived from a separate class of rare cells called tuft cells.
“We were using the CRISPR screen to discover new vulnerabilities in this disease that we didn’t know about before,” Vakoc says. “The surprise is that in the process, we discovered a new form of lung cancer.”
Patients with tumors that express high levels of this transcription factor, developing drugs that specifically target the function of POU2F3 may be particularly effective.
“In the past, we’ve lumped the different forms of SCLC together because they look similar on a microscope slide, but we now have some molecular tests that can easily discriminate these malignancies,” says postdoctoral investigator Yu-Han Huang, first author on the new paper. “Our findings suggest that we should be designing clinical studies for them separately, to find therapies that might cater to the different types of tumor.”
The researchers are currently looking for collaborators to do preclinical tests in mice to test compounds that target POU2F3. They are interested in using their CRISPR-based stress test to look for variant types of pancreas cancer which are thought to provide similar specific targets for treatments.